Irf1

Summary

Gene Symbol: Irf1
Description: interferon regulatory factor 1
Alias: AU020929, Irf-1, interferon regulatory factor 1
Species: mouse

Top Publications

  1. pmc Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression
    J C Blanco
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    J Exp Med 191:2131-44. 2000
  2. ncbi The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro
    Shuling Zhang
    Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201, USA
    J Endotoxin Res 8:379-88. 2002
  3. ncbi Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of interferon-gamma
    Ebru Karpuzoglu
    Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, 24061, USA
    Endocrinology 147:662-71. 2006
  4. ncbi Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes
    H Harada
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Cell 58:729-39. 1989
  5. ncbi Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1
    T Fujita
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Nature 337:270-2. 1989
  6. ncbi Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements
    M Miyamoto
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Cell 54:903-13. 1988
  7. ncbi Requirement for transcription factor IRF-1 in NO synthase induction in macrophages
    R Kamijo
    Department of Microbiology, New York University Medical Center, NY 10016
    Science 263:1612-5. 1994
  8. pmc Differential expression of interferon regulatory factor 1 (IRF-1), IRF-2, and interferon consensus sequence binding protein genes in lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive macrophages
    S A Barber
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 4788
    Infect Immun 63:601-8. 1995
  9. pmc Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes
    L F Reis
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    EMBO J 13:4798-806. 1994
  10. ncbi Involvement of the IRF-1 transcription factor in antiviral responses to interferons
    T Kimura
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Science 264:1921-4. 1994

Research Grants

Scientific Experts

Detail Information

Publications103 found, 100 shown here

  1. pmc Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression
    J C Blanco
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    J Exp Med 191:2131-44. 2000
    ..Our data demonstrate conclusively the importance of IFN-gamma as a direct activator and coactivator of the Cox-2 gene, and the central role of IRF-1/2 family members in this process...
  2. ncbi The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro
    Shuling Zhang
    Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 21201, USA
    J Endotoxin Res 8:379-88. 2002
    ..Collectively, these data provide evidence for an important role for IRF-1 in vivo and in vitro and for IRF-2 in vitro in the regulation of COX-2 expression by LPS...
  3. ncbi Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of interferon-gamma
    Ebru Karpuzoglu
    Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, 24061, USA
    Endocrinology 147:662-71. 2006
    ..These findings may have wide implications to immunity and inflammatory disorders including female-predominant autoimmune diseases...
  4. ncbi Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes
    H Harada
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Cell 58:729-39. 1989
    ..Our results suggest that transcription of the IFN and IFN-inducible genes is regulated by two similar trans-acting factors that apparently compete for the same cis-acting recognition sequences, but which have opposite effects...
  5. ncbi Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1
    T Fujita
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Nature 337:270-2. 1989
    ..This may be the first demonstration of the specific induction of silent chromosomal genes by transfection of a single transcription factor gene in mammalian cells...
  6. ncbi Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements
    M Miyamoto
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Cell 54:903-13. 1988
    ..Surprisingly, IRF-1 gene expression is dramatically induced by Newcastle disease virus in mouse L929 cells and by Concanavalin A in spleen cells. We show here that the IRF-1 gene possesses virus-inducible promoter...
  7. ncbi Requirement for transcription factor IRF-1 in NO synthase induction in macrophages
    R Kamijo
    Department of Microbiology, New York University Medical Center, NY 10016
    Science 263:1612-5. 1994
    ..Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice. Thus, IRF-1 is essential for iNOS activation in murine macrophages...
  8. pmc Differential expression of interferon regulatory factor 1 (IRF-1), IRF-2, and interferon consensus sequence binding protein genes in lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive macrophages
    S A Barber
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 4788
    Infect Immun 63:601-8. 1995
    ..Thus, the IRFs may represent yet an additional molecular pathway in the complex response to LPS...
  9. pmc Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes
    L F Reis
    Institut für Molekularbiologie I, Universitat Zurich, Switzerland
    EMBO J 13:4798-806. 1994
    The transcription factor interferon regulatory factor 1 (IRF-1) binds tightly to the interferon (IFN)-beta promoter and has been implicated in the induction of type I IFNs...
  10. ncbi Involvement of the IRF-1 transcription factor in antiviral responses to interferons
    T Kimura
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Science 264:1921-4. 1994
    ..Thus, IRF-1 is necessary for the antiviral action of IFNs against some viruses, but IFNs activate multiple activation pathways through diverse target genes to induce the antiviral state...
  11. ncbi Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development
    T Matsuyama
    Amgen Institute, University of Toronto, Ontario, Canada
    Cell 75:83-97. 1993
    b>Interferon regulatory factor 1 (IRF-1), a transcriptional activator, and its antagonistic repressor, IRF-2, were originally identified as regulators of the type I interferon (IFN) system...
  12. ncbi Differential dysregulation of nitric oxide production in macrophages with targeted disruptions in IFN regulatory factor-1 and -2 genes
    C A Salkowski
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 156:3107-10. 1996
    ..synthase mRNA in response to IFN-gamma and LPS. These results indicate that IRF-1 and IRF-2 differ in their mechanism of NO. regulation and that IRF-2 regulates inducible NO. synthase post-transcriptionally...
  13. ncbi Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies
    T Kimura
    Department of Immunology, Faculty of Medicine, University of Tokyo, Japan
    Genes Cells 1:115-24. 1996
    ..The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1)...
  14. ncbi Multistage regulation of Th1-type immune responses by the transcription factor IRF-1
    S Taki
    Department of Immunology, Faculty of Medicine, University of Tokyo, Japan
    Immunity 6:673-9. 1997
    ..These results indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response...
  15. ncbi The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes
    J M Penninger
    Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Immunity 7:243-54. 1997
    ..These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes...
  16. ncbi The role of IFN regulatory factor-1 in synovitis and nitric oxide production
    A Shiraishi
    Department of Medicine, University of California, San Diego, La Jolla 92093, USA
    J Immunol 159:3549-54. 1997
    ..These results indicate that IRF-1 has a tissue-specific role in the induction of iNOS. Inhibition of this transcription factor may represent a novel approach in controlling inflammatory diseases such as arthritis...
  17. pmc The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury
    C Iadecola
    Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Exp Med 189:719-27. 1999
    The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury...
  18. pmc Altered immune response of interferon regulatory factor 1-deficient mice against Plasmodium berghei blood-stage malaria infection
    R S Tan
    Molecular Parasitology Laboratory, Department of Biological Sciences, National University of Singapore, Singapore 119260, Singapore
    Infect Immun 67:2277-83. 1999
    ..In the present study, we used mice devoid of functional interferon regulatory factor 1 by targeted gene disruption (IRF-1(-/-)) to investigate the role of NO in the host immune response ..
  19. pmc Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53
    H Nozawa
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Bunkyo ku, Tokyo 113 0033, Japan
    Genes Dev 13:1240-5. 1999
    ..Our results suggest that IRF-1 is a new member of the tumor susceptibility genes...
  20. ncbi IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice
    C A Salkowski
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Immunol 163:1529-36. 1999
    ..These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production...
  21. ncbi An alternate pathway for type 1 T cell differentiation
    C Feng
    Department of Microbiology and Immunology, Ehime University School of Medicine, Shigenobu, Ehime 791 0295, Japan
    Int Immunol 11:1185-94. 1999
    ..This leads to the hypothesis that the IL-12-independent novel pathway for inducing IFN-gamma-producing T cells is distinct from the classical type 1/type 2 T cell subset differentiation pathway...
  22. ncbi The role of interferon regulatory factor-1 in cytokine-induced mRNA expression and cell death in murine pancreatic beta-cells
    D Pavlovic
    Eizirik, Department of Metabolism and Endocrinology, Diabetes Research Center, Laarbeeklaan 103, 1090 Brussels, Belgium
    Eur Cytokine Netw 10:403-12. 1999
    ..These effects are absent in purified beta-cells, suggesting that IRF-1 may mediate its effects on whole islets via activation of non-endocrine cells (e.g. macrophages and ductal cells) present in these preparations...
  23. ncbi Interferon regulatory factors: the next generation
    Y Mamane
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Canada
    Gene 237:1-14. 1999
    ..The aim of this review is to provide an update on the novel discoveries in the area of IRF transcription factors and the important roles of the new generation of IRFs--particularly IRF-3, IRF-4 and IRF-7...
  24. ncbi Protection against the mortality associated with disease models mediated by TNF and IFN-gamma in mice lacking IFN regulatory factor-1
    G Senaldi
    Amgen Inc, Thousand Oaks, CA 91320, USA
    J Immunol 163:6820-6. 1999
    ..The lack of IRF-1 appears to result in impaired production of TNF and IFN-gamma, reflecting a down-regulation of gene expression in the liver and spleen as well as a reduction in the number of splenic cells...
  25. pmc Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells
    M Lohoff
    Institut für Klinische Mikrobiologie und Immunologie, Universitat Erlangen, 91054 Erlangen, Germany
    J Exp Med 192:325-36. 2000
    ..Mechanistically, IRF-2 may act as a functional agonist rather than antagonist of IRF-1 for some, but not all, IFN-stimulated regulatory element (ISRE)-responsive genes...
  26. ncbi IRF family of transcription factors as regulators of host defense
    T Taniguchi
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Annu Rev Immunol 19:623-55. 2001
    ..Their functional roles, through interactions with their own or other members of the family of transcription factors, are becoming clearer in the regulation of host defense, such as innate and adaptive immune responses and oncogenesis...
  27. ncbi IRF-1 as a negative regulator of cell proliferation
    Giovanna Romeo
    Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy
    J Interferon Cytokine Res 22:39-47. 2002
    ....
  28. ncbi Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis
    Jinkyung Ko
    Laboratory of Cellular and Molecular Immunology, Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI 53706, USA
    J Immunol 168:2433-40. 2002
    ....
  29. ncbi Complex formation of the interferon (IFN) consensus sequence-binding protein with IRF-1 is essential for murine macrophage IFN-gamma-induced iNOS gene expression
    Huabao Xiong
    Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:2271-7. 2003
    ..Complex formation of ICSBP with IRF-1 is essential for iNOS expression, and interleukin-4 attenuates the physical interaction of ICSBP with IRF-1 resulting in the inhibition of INOS gene expression...
  30. ncbi Interferon regulatory factor 1 in mycobacterial infection
    Hiroyuki Yamada
    Department of Molecular Pathology, The Research Institute of Tuberculosis, Kiyose, Tokyo 204 0022, Japan
    Microbiol Immunol 46:751-60. 2002
    ..IRF-1 is indirectly responsible for iNOS mRNA expression and plays an important role in the pathogenesis of murine tuberculosis...
  31. pmc Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and interferon (IFN)-gamma-primed IL-12 production by IFN regulatory factor 1
    Jianguo Liu
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    J Exp Med 198:1265-76. 2003
    ..Thus, IRF-1 acts as a critical component of IFN-gamma signaling in the selective activation of IL-12 p35 transcription in synergy with LPS-mediated events...
  32. ncbi IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo
    Peter K M Kim
    Department of Surgery, University of Pittsburgh Medical Center, 497 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Oncogene 23:1125-35. 2004
    ..The mechanism of apoptosis may involve the transcriptional upregulation of bak, caspase-8, and caspase-7 expression. These data support the antitumor potential of IRF-1 and the use of agents that increase IRF-1 in breast cancer...
  33. ncbi Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein
    Jianguo Liu
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    J Biol Chem 279:55609-17. 2004
    ..This study provides novel mechanistic information on how signals initiated during innate and adaptive immune responses synergize to yield greater IL-12 production and sustained cellular immunity...
  34. ncbi IRF-7 is the master regulator of type-I interferon-dependent immune responses
    Kenya Honda
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 434:772-7. 2005
    ..Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7...
  35. ncbi Interferon regulatory factor 1 is an essential and direct transcriptional activator for interferon {gamma}-induced RANTES/CCl5 expression in macrophages
    Jianguo Liu
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 280:24347-55. 2005
    b>Interferon regulatory factor 1 (IRF-1) is an important transcription factor in interferon gamma (IFNgamma)-mediated signaling in the development and function of NK cells and cytotoxic T lymphocytes...
  36. ncbi IRF-1 and NF-kappaB p50/cRel bind to distinct regions of the proximal murine IL-12 p35 promoter during costimulation with IFN-gamma and LPS
    Jutta I Kollet
    Department of Oral Biology and the Nebraska Center for Virology, University of Nebraska Medical Center, Lincoln, NE 68583 0740, USA
    Mol Immunol 43:623-33. 2006
    ..Thus, cRel with IRF-1 induce p35 expression through a small region of the p35 exon 2 promoter during IFN-gamma and LPS costimulation of macrophages...
  37. ncbi IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features
    L Gabriele
    Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Viale Regina Elena, 299, Rome 00161, Italy
    J Leukoc Biol 80:1500-11. 2006
    ..Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells...
  38. pmc Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program
    Hideo Negishi
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Proc Natl Acad Sci U S A 103:15136-41. 2006
    ..In this study we demonstrate that IRF1, which is induced by IFN-gamma, also interacts with and is activated by MyD88 upon TLR activation...
  39. ncbi Interferon-regulatory-factor 1 controls Toll-like receptor 9-mediated IFN-beta production in myeloid dendritic cells
    Frank Schmitz
    Institute for Medical Microbiology, Immunology and Hygiene, Munich, Germany
    Eur J Immunol 37:315-27. 2007
    ..These results demonstrate that TLR-9 activation of mDC and macrophages contributes to antiviral immunity via IRF-1...
  40. pmc Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene
    Katrin Ramsauer
    Max F Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, A1030 Vienna, Austria
    Proc Natl Acad Sci U S A 104:2849-54. 2007
    A subgroup of genes induced by IFN-gamma requires both STAT1 and IRF1 for transcriptional activation. Using WT, stat1(-/-), or irf1(-/-) cells, we analyzed the changes induced by IFN-gamma in gbp2 promoter chromatin...
  41. ncbi The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells
    Shin ichi Kano
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nat Immunol 9:34-41. 2008
    ..Here we show that the IFN-gamma-induced transcription factor IRF1 was essential in T(H)1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor beta1 subunit (IL-..
  42. ncbi IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression
    Alessandra Fragale
    Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita, Rome, Italy
    J Immunol 181:1673-82. 2008
    ..We conclude that IRF-1 is a key negative regulator of CD4(+)CD25(+) Treg cells through direct repression of Foxp3 expression...
  43. ncbi IFN-gamma-induced TNF-alpha expression is regulated by interferon regulatory factors 1 and 8 in mouse macrophages
    Virginia Vila-del Sol
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, C Nicolás Cabrera, 1 Campus Cantoblanco, Universidad Autonoma de Madrid, Madrid, Spain
    J Immunol 181:4461-70. 2008
    ..In summary, IFN-gamma treatment induces TNF-alpha expression at transcriptional level requiring the coordinate action of IRF-1 and IRF-8...
  44. doi Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells
    Giuseppe Mancuso
    The Elie Metchnikoff Department, University of Messina, Messina, Italy
    Nat Immunol 10:587-94. 2009
    ..dendritic cells by a mechanism that required Toll-like receptor 7, the adaptor MyD88 and the transcription factor IRF1, all of which localized together with bacterial products in degradative vacuoles bearing lysosomal markers...
  45. pmc Restriction of Legionella pneumophila replication in macrophages requires concerted action of the transcriptional regulators Irf1 and Irf8 and nod-like receptors Naip5 and Nlrc4
    Anne Fortier
    Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Room 907, Montreal, Quebec, Canada H3G 1Y6
    Infect Immun 77:4794-805. 2009
    ..pneumophila infection suggested that two members of the Irf transcriptional regulator family, Irf1 and Irf8, are regulated in response to Naip5 sensing of L. pneumophila...
  46. doi IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction
    Anja Stirnweiss
    Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany
    J Immunol 184:5179-85. 2010
    ..This mechanism becomes important when viruses evade innate immunity by antagonizing the induction and function of the IFN system...
  47. pmc Peroxisomes are signaling platforms for antiviral innate immunity
    Evelyn Dixit
    Division of Gastroenterology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Cell 141:668-81. 2010
    ..The interferon regulatory factor IRF1 plays a crucial role in regulating MAVS-dependent signaling from peroxisomes...
  48. doi IRF-1 expression is essential for natural killer cells to suppress metastasis
    Antje Ksienzyk
    Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany
    Cancer Res 71:6410-8. 2011
    ..Taken together, our findings establish IRF-1 as an essential mediator of the cross-talk between tumor cells and NK cells that mediate immune surveillance in the metastatic niche...
  49. pmc Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection
    James D Brien
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Pathog 7:e1002230. 2011
    ..Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8(+) T cell response...
  50. pmc Endothelial TNF receptor 2 induces IRF1 transcription factor-dependent interferon-β autocrine signaling to promote monocyte recruitment
    Deepak Venkatesh
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Immunity 38:1025-37. 2013
    ..The TNF receptors signaled through interferon regulatory factor-1 (IRF1) to induce interferon-β (IFN-β) and subsequent autocrine signaling via the type I IFN receptor and the ..
  51. ncbi Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1-/- mice
    L C White
    University of North Carolina Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill 27599, USA
    Immunity 5:365-76. 1996
    ..The role of IRF-1 in the regulation of TAP1 and LMP2 suggests a mechanism for the antiviral properties of IRF-1 and the unexpected deficiency of CD8+ T cells observed in IRF-1-/- mice...
  52. ncbi Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter
    Saho Maruyama
    Department of Immunology and Host Defenses, Ehime University School of Medicine, Shigenobu, Japan
    J Immunol 170:997-1001. 2003
    ..While IFN-gamma must be present for IL-12 p40 gene induction, the p35 gene is strongly induced by LPS, even in the absence of IFN-gamma, and therefore the induction of the p35 gene is IRF-1 independent...
  53. ncbi Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system
    N Tanaka
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Adv Immunol 52:263-81. 1992
  54. ncbi IRF-1: the transcription factor linking the interferon response and oncogenesis
    T Taniguchi
    Department of Immunology, Faculty of Medicine, University of Tokyo Hongo, Japan
    Biochim Biophys Acta 1333:M9-17. 1997
  55. pmc An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes
    P H Driggers
    Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 87:3743-7. 1990
    ..The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression...
  56. ncbi IL-2-induced proliferative response is controlled by loci Cinda1 and Cinda2 on mouse chromosomes 11 and 12: a distinct control of the response induced by different IL-2 concentrations
    M Krulova
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Genomics 42:11-5. 1997
    ..Understanding the action of genetic factors, such as Cinda1 and Cinda2, that control T cell function is expected to contribute to the efficient analysis of the genetic control of susceptibility to infections and autoimmune diseases...
  57. ncbi Thymic heterotypic cellular complexes in gene-targeted mice with defined blocks in T cell development and adhesion molecule expression
    A J Oliveira-dos-Santos
    Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria
    Eur J Immunol 28:2882-92. 1998
    ..These results provide genetic evidence on the role of defined stages in T cell development and adhesion molecules on thymocyte/stromal cell interactions in vitro...
  58. ncbi The role of STAT1/IRF-1 on synergistic ROS production and loss of mitochondrial transmembrane potential during hepatic cell death induced by LPS/d-GalN
    Hyun Jung Lee
    Division of Intractable Diseases, Center for Biomedical Sciences, National Institutes of Health, Eunpyeong gu, Seoul, South Korea
    J Mol Biol 369:967-84. 2007
    ..cells compared with cells treated with IFN-gamma alone, the absence of STAT1 or interferon regulatory factor 1 (IRF-1) in genetic knockout mice strongly abrogated the observed effects of TNF-alpha/IFN-gamma on ..
  59. doi Ubc9-mediated sumoylation leads to transcriptional repression of IRF-1
    Eun Joo Kim
    Department of Molecular Biology, Dankook University, Gyeonggi do 448 701, Republic of Korea
    Biochem Biophys Res Commun 377:952-6. 2008
    ..Taken together, these observations suggest that Ubc9 functions as a transcriptional repressor of IRF-1 by inducing sumoylation, and that this effect may be required for the physiological activity of IRF-1...
  60. pmc Interferon regulatory factor-1 in flagellin-induced reprogramming: potential protective role of CXCL10 in cornea innate defense against Pseudomonas aeruginosa infection
    Gi Sang Yoon
    Department of Anatomy and Cell Biology, Kresge Eye Institute, Wayne State University, Detroit, Michigan
    Invest Ophthalmol Vis Sci 54:7510-21. 2013
    ..Thus, we sought to determine the role of one transcription factor, interferon regulatory factor (IRF1), and its target gene CXCL10 therein.
  61. pmc Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA
    Kazuya Masuda
    Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565 0871, Japan
    J Exp Med 213:605-19. 2016
    ..These cells displayed the feature of antiinflammatory (Il10-expressing) CD4(+)T cells. Thus, we show a T cell-intrinsic role of Arid5a on fate decisions of naive CD4(+)T cells through selective stabilization of Stat3 mRNA...
  62. pmc Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription
    Hideki Hayashi
    Division of Cytokine Signaling, Department of Molecular Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852 8523, Japan
    Proc Natl Acad Sci U S A 108:18766-71. 2011
    ..We speculate that Trypsin5, the trypsinogen5 gene product, leaking from dead acinar cells triggers a chain reaction leading to lethal pancreatitis in Irf2(-/-) mice because it is resistant to a major endogenous trypsin inhibitor, Spink3...
  63. pmc C7L family of poxvirus host range genes inhibits antiviral activities induced by type I interferons and interferon regulatory factor 1
    Xiangzhi Meng
    Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
    J Virol 86:4538-47. 2012
    ..Screening of a library of more than 350 IFN-stimulated genes (ISGs) identified interferon-regulated factor 1 (IRF1) as an inhibitor of vK1L(-)C7L(-) but not wild-type VACV...
  64. pmc Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNβ in mouse pancreatic β-cells
    Wieke Freudenburg
    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America
    PLoS ONE 8:e52408. 2013
    ..case the expression is transient, with maximal mRNA accumulation in 12 hours, and depends primarily on Interferon Regulatory Factor 1. IFNs do not alter expression of regular proteasome genes, and in the time frame of IFNβ-mediated ..
  65. pmc 5' upstream sequences of MyD88, an IL-6 primary response gene in M1 cells: detection of functional IRF-1 and Stat factors binding sites
    S Harroch
    Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel
    Nucleic Acids Res 23:3539-46. 1995
    ..b>IRF1, an activator of transcription, is also induced to bind to this sequence at later times...
  66. ncbi iNOS expression and nitrotyrosine formation in the myocardium in response to inflammation is controlled by the interferon regulatory transcription factor 1
    K Bachmaier
    Amgen Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, Canada
    Circulation 96:585-91. 1997
    ....
  67. ncbi Cytokine-dependent abortion in CBA x DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase [correction of prothombinase]
    D A Clark
    McMaster University, Hamilton, Ontario, Canada
    J Immunol 160:545-9. 1998
    ..The cytokines also aborted IRF1+/+ C57BL/6 but not IRF1-/- females pregnant by IRF1+/+ DBA/2...
  68. ncbi Interferon regulatory transcription factors are constitutively expressed and spatially regulated in the mouse lens
    W Li
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA
    Dev Biol 210:44-55. 1999
    ....
  69. pmc Genomic interval engineering of mice identifies a novel modulator of triglyceride production
    Y Zhu
    Genome Sciences Department, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 97:1137-42. 2000
    ....
  70. ncbi Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure
    K Streetz
    Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany
    J Immunol 167:514-23. 2001
    ..Therefore, our experiments indicate that 11418690..
  71. ncbi Developmental and functional defects of thymic and epidermal V gamma 3 cells in IL-15-deficient and IFN regulatory factor-1-deficient mice
    An De Creus
    Department of Clinical Chemistry, Microbiology, and Immunology, University of Ghent, University Hospital, Ghent, Belgium
    J Immunol 168:6486-93. 2002
    ..Furthermore, a possible role for IRF-1 in inducing morphological maturation of DETCs and cytolytic capacity of V gamma 3 cells is suggested...
  72. ncbi IFN regulatory factor-1 is required for the up-regulation of the CD40-NF-kappa B activator 1 axis during airway inflammation
    Zhendong Zhao
    Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Immunol 170:5674-80. 2003
    ..The induced expression of the CD40-Act1 axis by inflammatory cytokines in epithelial cells probably plays an important role in priming these cells for their response to CD40 ligand during airway inflammation...
  73. ncbi Assessment of requirements for IL-15 and IFN regulatory factors in uterine NK cell differentiation and function during pregnancy
    Ali A Ashkar
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
    J Immunol 171:2937-44. 2003
    ..These studies indicate that uNK cell development and maturation share some aspects with NK cell development in other tissues, but also display distinctive tissue-specific regulation...
  74. ncbi Deregulated expression of interferon regulatory factor-1 in oncogene-transformed mouse fibroblasts
    Sara Contente
    United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Interferon Cytokine Res 23:639-47. 2003
    ..A mainly cytoplasmic, constitutively expressed 46-kDa protein with immunologic identity to the 43-kDa nuclear IRF-1 was also present in normal and transformed cells, but as it did not bind to the IRF elements, its function is unclear...
  75. ncbi Defective clearance of adenovirus in IRF-1 mice associated with defects in NK and T cells but not macrophages
    X Xu
    Department of Medicine, The University of Alabama at Birmingham, 701 S 19th Street, Birmingham, AL 35294 0007, USA
    Scand J Immunol 60:89-99. 2004
    ..These results indicate that delayed clearance of Ad is associated with partial correction of defects of the NK, NK-T and CD8 T cells and increased production of IFN-gamma and IL-18 in IRF-1(-/-) mice...
  76. ncbi Expression and DNA binding activity of the recombinant interferon regulatory factor-1 (IRF-1) of mouse
    Meenakshi Upreti
    Molecular Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Mol Biol Rep 32:103-16. 2005
    ..Specificity of DNA binding by IRF-1 lies in the 5th and 6th nucleotides in the GAAAGT sequence. Multiple IRF-1-DNA complexes should stimulate transcription by IRF-1...
  77. pmc Interferon function is not required for recovery from a secondary poxvirus infection
    Vijay Panchanathan
    Infection and Immunity Group, Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
    Proc Natl Acad Sci U S A 102:12921-6. 2005
    ..Importantly, the depletion of CD8+ T lymphocytes during a secondary challenge in IFN-deficient mice does not affect their capacity to clear ECTV, indicating that Ab is critical for the control of a secondary infection...
  78. ncbi Histone acetylation regulates the cell type specific CIITA promoters, MHC class II expression and antigen presentation in tumor cells
    Shiuh Dih Chou
    Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Int Immunol 17:1483-94. 2005
    ....
  79. ncbi Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells
    Pedro A Ruiz
    Else Kroener Fresenius Centre for Experimental Nutritional Medicine, Technical University of Munich, Freising Weihenstephan, Germany
    J Nutr 136:664-71. 2006
    ....
  80. ncbi IFN-gamma upregulates expression of the mouse complement C1rA gene in keratinocytes via IFN-regulatory factor-1
    Sung June Byun
    National Livestock Research Institute, Division of Animal Biotechnology, Suwon, South Korea
    J Invest Dermatol 127:1187-96. 2007
    ..We conclude that IFN-gamma stimulates mC1rA gene expression via IRF-1 in mouse keratinocytes...
  81. pmc STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice
    Zan Huang
    Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    J Clin Invest 117:3890-9. 2007
    ..Our studies elucidate potential mechanisms by which various inflammatory disorders can cause elevated platelet counts...
  82. doi Adenylate cycalse toxin of Bordetella pertussis inhibits TLR-induced IRF-1 and IRF-8 activation and IL-12 production and enhances IL-10 through MAPK activation in dendritic cells
    Fionnuala B Hickey
    Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
    J Leukoc Biol 84:234-43. 2008
    ....
  83. pmc Transcriptional regulation of mouse L-selectin
    Xitong Dang
    Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
    Biochim Biophys Acta 1789:146-52. 2009
    ..Site-directed mutagenesis and chromatin immunoprecipitation showed that Mzf1, Klf2, Sp1, Ets1, and Irf1 bind to and activate the mouse sell promoter...
  84. doi Kinetic of RelA activation controls magnitude of TLR-mediated IL-12p40 induction
    Konrad A Bode
    Department of Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany
    J Immunol 182:2176-84. 2009
    ..It is suggested that differences in the kinetics of a common TLR signaling module affect the biological response patterns of various TLRs, with IL-12p40 being a gene that needs prolonged NF-kappaB activation...
  85. pmc IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice
    Qianli Yu
    Surgery Department and Sarver Heart Center, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
    Am J Physiol Heart Circ Physiol 297:H76-85. 2009
    ..Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts...
  86. pmc Murine toll-like receptor 2 activation induces type I interferon responses from endolysosomal compartments
    Nicole Dietrich
    Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
    PLoS ONE 5:e10250. 2010
    ..Until now, TLR2 activation by bacterial ligands has long been associated with pro-inflammatory cytokines but not type I interferon responses...
  87. ncbi Molecular cloning of interferon-gamma inducible genes from a murine pre-B cell leukemia
    G Gribaudo
    Institute of Microbiology, Medical School, University of Torino, Italy
    J Biol Regul Homeost Agents 6:137-41. 1992
    ..Taken as a whole, these results demonstrate that in leukemic pre-B cells IFN-gamma induces the expression of a gene that could be employed as specific cell activation marker...
  88. ncbi Localization of the human chromosome 5q genes Gabra-1, Gabrg-2, Il-4, Il-5, and Irf-1 on mouse chromosome 11
    M S Buckwalter
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109 0618
    Mamm Genome 3:604-7. 1992
  89. ncbi Abrogation of G1 arrest after DNA damage is associated with constitutive overexpression of Mdm2, Cdk4, and Irf1 mRNAs in the BALB/c 3T3 A31 variant 1-1 clone
    T Nozaki
    Department of Oral and Maxillo Facial Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo ku, Japan
    Biochem Biophys Res Commun 233:216-20. 1997
    ..In addition, overexpression of a growth-suppressive transcription factor, Irf1, a putative key molecule in the p53-independent pathway after DNA damage, was also observed, although the relation ..
  90. ncbi Computational and biological analysis of 680 kb of DNA sequence from the human 5q31 cytokine gene cluster region
    K A Frazer
    Human Genome Center, Lawrence Berkeley National Laboratory LBNL, Berkeley, California 94720, USA
    Genome Res 7:495-512. 1997
    ....
  91. ncbi Structure of IRF-1 with bound DNA reveals determinants of interferon regulation
    C R Escalante
    Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nature 391:103-6. 1998
    ..Together, these features suggest a basis for the occurrence of GAAA repeats within IRF response elements and provide clues to the assembly of the higher-order interferon-beta enhancesome...
  92. ncbi Tpm1, a locus controlling IL-12 responsiveness, acts by a cell-autonomous mechanism
    M L Guler
    Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 162:1339-47. 1999
    ..This result strongly implies that despite the proximity of our locus to the IL-13/IL-4 gene cluster, these cytokines are not candidates for Tpm1...
  93. ncbi Identification of 40 genes on a 1-Mb contig around the IL-4 cytokine family gene cluster on mouse chromosome 11
    S E Wenderfer
    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267 0524, USA
    Genomics 63:354-73. 2000
    ..The integrated physical and transcript maps should prove valuable as a complement to genomic sequencing and expression-dependent transcript maps of this segment of the genome...
  94. ncbi Bax gene disruption alters the epidermal response to ultraviolet irradiation and in vivo induced skin carcinogenesis
    S H Cho
    Department of Molecular Pathology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Int J Mol Med 7:235-41. 2001
    ....
  95. ncbi Overexpression of Bcl-2 differentially restores development of thymus-derived CD4-8+ T cells and intestinal intraepithelial T cells in IFN-regulatory factor-1-deficient mice
    T Ohteki
    Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    J Immunol 166:6509-13. 2001
    ..Our results indicate that IRF-1 differentially regulates the development of these lymphocyte subsets and that survival signals involving Bcl-2 are critical for the development of thymus-dependent CD8+ T cells...
  96. pmc Pulmonary inflammation induced by Pseudomonas aeruginosa lipopolysaccharide, phospholipase C, and exotoxin A: role of interferon regulatory factor 1
    Catharina W Wieland
    Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Infect Immun 70:1352-8. 2002
    ..These data indicate that different virulence factors from P. aeruginosa induce pulmonary inflammation in vivo and that IRF-1 is involved in some of the cytokine responses to LPS and ETA...
  97. ncbi Development of CD30+ lymphoproliferative disease in mice lacking interferon regulatory factor-1
    Donna D Eason
    Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA
    Oncogene 22:6166-76. 2003
    ..This mouse model will also be useful in testing therapies for different forms of CD30+ lymphoma, in particular anti-CD30-based therapies...
  98. pmc Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFN gamma-inducible fibrinogen-like protein 2
    Wayne W Hancock
    Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 101:3005-10. 2004
    ..gondii infection and allograft rejection. Together, our findings suggest that Fgl2, although highly conserved and IFN gamma-inducible, is not a critical mediator of either type 1 immunity or immune-associated coagulant activity...
  99. ncbi Modulation of T cell development and activation by novel members of the Schlafen (slfn) gene family harbouring an RNA helicase-like motif
    Peter Geserick
    Department of Immunology, Max Planck Institute for Infection Biology, Schumannstr 21 22, 10117 Berlin, Germany
    Int Immunol 16:1535-48. 2004
    ..Thus, functional participation of slfn8 in the regulatory networks governing T cell development and growth appears to be cell type specific...
  100. ncbi Altered phenotype of dextran sulfate sodium colitis in interferon regulatory factor-1 knock-out mice
    Elizabeth E Mannick
    Louisiana State University, Stanley S Scott Cancer Center, LA, USA
    J Gastroenterol Hepatol 20:371-80. 2005
    ..We examined the role of IRF-1 in dextran sulfate sodium colitis, a murine model of inflammatory bowel disease, to determine if absence of the gene would protect against colitis...
  101. ncbi The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury
    Allan Tsung
    Department of Surgery, University of Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 290:G1261-8. 2006
    ..We further show that IRF-1-mediated injury involves the activation of JNK and that hepatocellular IRF-1 expression itself is regulated by specific cytokines...

Research Grants2

  1. ALTERED EPITHELIAL STAT1 DEPENDENT SIGNALING IN CYSTIC F
    Thomas Kelley; Fiscal Year: 2003
    ..Learning how a loss of CFTR function leads to altered cell signaling processes and how these processes unfluence disease may increase our understanding of CF and lead to more precise therapeutic interventions. ..
  2. Cholesterol transport regulation in cystic fibrosis
    Thomas Kelley; Fiscal Year: 2007
    ..Aim 3. To examine isoprenoid/cholesterol synthesis and sterol regulatory element binding protein-1 (SREBP-1a and SREBP-1c) and SREBP-2 regulation in CF cells. [unreadable] [unreadable]..