M F Smith

Summary

Affiliation: University of Virginia
Country: USA

Publications

  1. ncbi Secretory interleukin-1 receptor antagonist gene expression requires both a PU.1 and a novel composite NF-kappaB/PU.1/ GA-binding protein binding site
    M F Smith
    Department of Medicine, Division of Gastroenterology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
    J Biol Chem 273:24272-9. 1998
  2. ncbi Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells
    Michael F Smith
    University of Virginia Health System, Digestive Health Center of Excellence and Department of Microbiology, Charlottesville, Virginia 22908 0708, USA
    J Biol Chem 278:32552-60. 2003
  3. ncbi Helicobacter pylori and toll-like receptor agonists induce syndecan-4 expression in an NF-kappaB-dependent manner
    Michael F Smith
    Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908 0708, USA
    Glycobiology 16:221-9. 2006
  4. ncbi Microbial-induced regulation of syndecan expression: important host defense mechanism or an opportunity for pathogens?
    Michael F Smith
    Department of Medicine, Digestive Health Center of Excellence and Microbiology, University of Virginia Health System, Charlottesville, VA, USA
    ScientificWorldJournal 6:442-5. 2006
  5. ncbi The human intracellular interleukin 1 receptor antagonist promoter appropriately regulates gene expression in keratinocytes and gastrointestinal epithelial cells in vivo
    C Gabay
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Cytokine 11:561-70. 1999
  6. ncbi Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein
    C Gabay
    Division of Rheumatology, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Clin Invest 99:2930-40. 1997
  7. ncbi Toll-like receptor 2 and 4 (TLR2 and TLR4) agonists differentially regulate secretory interleukin-1 receptor antagonist gene expression in macrophages
    Virginia S Carl
    Digestive Health Center of Excellence and Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    J Biol Chem 277:17448-56. 2002
  8. ncbi Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression
    Kieran A Ryan
    Digestive Health Center of Excellence, University of Virginia, Charlottesville, Virginia 22908, USA
    Infect Immun 72:2123-30. 2004
  9. ncbi Toll-like receptor 2-mediated gene expression in epithelial cells during Helicobacter pylori infection
    Song-Ze Ding
    Department of Microbiology, The University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
    Helicobacter 10:193-204. 2005
  10. ncbi MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling
    Molly A Hughes
    Department of Internal Medicine, Division of Infectious Diseases, University of Virginia Health Sciences System, P O Box 800513, Charlottesville, VA 22908, USA
    Infect Immun 73:7535-40. 2005

Research Grants

  1. IDENTIFICATION OF LPS-INDUCED SIGNALING MECHANISMS
    Michael Smith; Fiscal Year: 2004
  2. Gastric Epithelial-specific Gene Targeting
    Michael Smith; Fiscal Year: 2005

Collaborators

Detail Information

Publications26

  1. ncbi Secretory interleukin-1 receptor antagonist gene expression requires both a PU.1 and a novel composite NF-kappaB/PU.1/ GA-binding protein binding site
    M F Smith
    Department of Medicine, Division of Gastroenterology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
    J Biol Chem 273:24272-9. 1998
    ..1 binding sites are the major response elements for LPS-induced IL-1Ra gene expression...
  2. ncbi Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells
    Michael F Smith
    University of Virginia Health System, Digestive Health Center of Excellence and Department of Microbiology, Charlottesville, Virginia 22908 0708, USA
    J Biol Chem 278:32552-60. 2003
    ..These studies demonstrate that gastric epithelial cells recognize and respond to H. pylori infection at least in part via TLR2 and TLR5. Furthermore, the unique lipopolysaccharide of H. pylori is a TLR2, not a TLR4 agonist...
  3. ncbi Helicobacter pylori and toll-like receptor agonists induce syndecan-4 expression in an NF-kappaB-dependent manner
    Michael F Smith
    Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908 0708, USA
    Glycobiology 16:221-9. 2006
    ..pylori and TLR agonists. These results thus demonstrate that the response of the syndecan-4 gene to infectious agents, or their products, is a direct result of NF-kappaB binding to the promoter and induction of de novo transcription...
  4. ncbi Microbial-induced regulation of syndecan expression: important host defense mechanism or an opportunity for pathogens?
    Michael F Smith
    Department of Medicine, Digestive Health Center of Excellence and Microbiology, University of Virginia Health System, Charlottesville, VA, USA
    ScientificWorldJournal 6:442-5. 2006
  5. ncbi The human intracellular interleukin 1 receptor antagonist promoter appropriately regulates gene expression in keratinocytes and gastrointestinal epithelial cells in vivo
    C Gabay
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Cytokine 11:561-70. 1999
    ..However, other as yet unidentified regulatory regions influence icIL-1Ra gene expression in macrophages following LPS stimulation...
  6. ncbi Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein
    C Gabay
    Division of Rheumatology, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Clin Invest 99:2930-40. 1997
    ..In addition, NF-kappaB and C/EBP family members are likely to play important roles in the full expression of IL-1Ra by hepatocytes during inflammatory conditions...
  7. ncbi Toll-like receptor 2 and 4 (TLR2 and TLR4) agonists differentially regulate secretory interleukin-1 receptor antagonist gene expression in macrophages
    Virginia S Carl
    Digestive Health Center of Excellence and Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    J Biol Chem 277:17448-56. 2002
    ..Collectively, these data indicated that while some of the intracellular signaling events by TLR2 and TLR4 agonists are similar, there are clearly distinct differences in the responses elicited by these two bacterial products...
  8. ncbi Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression
    Kieran A Ryan
    Digestive Health Center of Excellence, University of Virginia, Charlottesville, Virginia 22908, USA
    Infect Immun 72:2123-30. 2004
    ..These data provide evidence that ROS regulate immune signaling through TLR4 via their effects on NF-kappa B activation...
  9. ncbi Toll-like receptor 2-mediated gene expression in epithelial cells during Helicobacter pylori infection
    Song-Ze Ding
    Department of Microbiology, The University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
    Helicobacter 10:193-204. 2005
    ..This approach will be helpful in identifying genes whose expression is mediated by specific TLRs and in determining the cellular responses that are responsible for diverse signal pathways during H. pylori infection...
  10. ncbi MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling
    Molly A Hughes
    Department of Internal Medicine, Division of Infectious Diseases, University of Virginia Health Sciences System, P O Box 800513, Charlottesville, VA 22908, USA
    Infect Immun 73:7535-40. 2005
    ..We conclude that, although recognition of B. anthracis occurs via TLR2, additional MyD88-dependent pathways contribute to the host innate immune response to anthrax infection...
  11. ncbi Magnetic resonance imaging of gastric cancer in Tff1 knock-out mice
    Stuart S Berr
    Department of Radiology, University of Virginia, Charlottesville 22908, USA
    Magn Reson Med 49:1033-6. 2003
    ..The stomach of the Tff1 -/- mouse demonstrates a thickened wall; a jagged, irregular surface; and protruding nodules that are bright after injection of Gd-DTPA...
  12. ncbi Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP
    Wa el El-Rifai
    Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
    Cancer Res 62:4061-4. 2002
    ..Our results reveal for the first time the presence of these signaling molecules in human cancer and suggest that they may be important for gastric tumorigenesis...
  13. ncbi Role of endogenous IL-10 in LPS-induced STAT3 activation and IL-1 receptor antagonist gene expression
    Virginia S Carl
    University of Virginia Health System, Department of Medicine, Digestive Health Center of Excellence and Microbiology, Charlottesville, VA 22908 0708, USA
    J Leukoc Biol 76:735-42. 2004
    ..Together, these results demonstrate that endogenously produced IL-10 plays a significant role in LPS-induced sIL-1Ra gene expression via the activation of STAT3...
  14. ncbi Roles of intracellular calcium and NF-kappa B in the Clostridium difficile toxin A-induced up-regulation and secretion of IL-8 from human monocytes
    K K Jefferson
    Department of Medicine, Health Sciences Center, University of Virginia, Charlottesville 22908, USA
    J Immunol 163:5183-91. 1999
    ..difficile toxin-mediated up-regulation of IL-8 synthesis and release by target cells. This information should increase our understanding of the pathogenesis of C. difficile colitis and the nature of IL-8 gene regulation as well...
  15. ncbi IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells
    T T Pizarro
    Department of Medicine, Digestive Health Center, University of Virginia Health Sciences Center, Charlottesville 22908, USA
    J Immunol 162:6829-35. 1999
    ..In addition, our studies further support the concept that IEC and dendritic cells may possess important immunoregulatory functions in both normal, as well as pathological, mucosal immunity...
  16. ncbi Intracellular IL-1 receptor antagonist promoter: cell type-specific and inducible regulatory regions
    J K Jenkins
    Division of Rheumatology, Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA
    J Immunol 158:748-55. 1997
    ..However, our results indicate that the ability of this proximal promoter region to control expression is strongly influenced, both positively and negatively, by other upstream cis-acting elements in a cell type-specific manner...
  17. ncbi Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1
    Asima Bhattacharyya
    Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA
    J Immunol 177:7990-9. 2006
    ..By implicating APE-1/Ref-1 as an important regulator of gastric epithelial responses to H. pylori infection, these data elucidate a novel mechanism controlling transcription and gene expression in bacterial pathogenesis...
  18. ncbi Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells
    Song Ze Ding
    Department of Microbiology, The University of Virginia Health System, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA
    FEMS Immunol Med Microbiol 53:385-94. 2008
    ..These results provide more insight into how H. pylori and MAPK modulate AP-1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions...
  19. ncbi Differential ex vivo nitric oxide production by acutely isolated neonatal and adult microglia
    John B Schell
    Departments of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
    J Neuroimmunol 189:75-87. 2007
    ..Finally, we demonstrate that the differential nitric oxide response of neonatal and adult microglia is not only limited to the mouse, but also extends to rat microglia...
  20. ncbi Helicobacter pylori and mitogen-activated protein kinases regulate the cell cycle, proliferation and apoptosis in gastric epithelial cells
    Song Ze Ding
    Department of Microbiology, The University of Virginia Health System, Charlottesville, Virginia 22908 0734, USA
    J Gastroenterol Hepatol 23:e67-78. 2008
    ..Therefore, we investigated the effects of H. pylori infection and MAPK inhibition on these processes...
  21. ncbi Structural and functional evidence for the role of the TLR2 DD loop in TLR1/TLR2 heterodimerization and signaling
    Jitendra K Gautam
    Departments of Medicine, Digestive Health Center of Excellence, and Microbiology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    J Biol Chem 281:30132-42. 2006
    ..Additionally, mutation of an amino acid residue (TLR2 Asp-730) in Region II also resulted in decreased activity in agreement with our model, providing new insights into the structure-function relationship of TLR2/1 TIR domains...
  22. ncbi Identification of a quantitative trait locus for ileitis in a spontaneous mouse model of Crohn's disease: SAMP1/YitFc
    Kosuke Kozaiwa
    Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
    Gastroenterology 125:477-90. 2003
    ..We performed a genetic analysis of a (B6 x SAMP1/Fc)F(2) cross to localize the genes regulating intestinal inflammation in this model...
  23. ncbi Hypermethylation of metallothionein-3 CpG island in gastric carcinoma
    Dajun Deng
    Peking University Health Science Center and Beijing Institute for Cancer Research, Beijing, 100034, China
    Carcinogenesis 24:25-9. 2003
    ..007). In conclusion, the CpG island in the MT-3 intron1 are abnormally hypermethylated in many gastric carcinomas and may account for the downregulation of MT-3 in gastric carcinogenesis...
  24. ncbi Characterization of gelatinases in bronchoalveolar lavage fluid and gelatinases produced by alveolar macrophages isolated from healthy calves
    Jeffrey Lakritz
    Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA
    Am J Vet Res 65:163-72. 2004
    ..Lipopolysaccharide-stimulated alveolar macrophages express MMP-9 but not MMP-2 mRNA. The role of proteases in the pathogenesis of lung injury associated with pneumonia has yet to be determined...
  25. ncbi Analysis of luteal tissue inhibitor of metalloproteinase-1, -2, and -3 during prostaglandin F(2alpha)-induced luteolysis
    William A Ricke
    Department of Animal Science, 160 Animal Science Center, University of Missouri, Columbia, MO 65211, USA
    Biol Reprod 66:1387-94. 2002
    ..This action may increase the MMP:TIMP-1 ratio, creating an environment that favors extracellular matrix degradation and, thereby, facilitates both functional and structural regression...
  26. ncbi Simultaneous detection of CpG methylation and single nucleotide polymorphism by denaturing high performance liquid chromatography
    Dajun Deng
    Peking University School of Oncology and Beijing Institute for Cancer Research, Beijing, 100034, China
    Nucleic Acids Res 30:E13. 2002
    ..In conclusion, methylation in homoallelic and heteroallelic CpG islands could be detected rapidly and reliably by bisulfite-DHPLC. A SNP in the target sequence could also be detected at the same time...

Research Grants7

  1. IDENTIFICATION OF LPS-INDUCED SIGNALING MECHANISMS
    Michael Smith; Fiscal Year: 2004
    ..4 and B1.7 kb upstream of the transcription start site of the sIL-1Ra gene and develop a transgenic mouse model in order to study the role of the distal enhancer element in the regulation of gene expression in vivo. ..
  2. Gastric Epithelial-specific Gene Targeting
    Michael Smith; Fiscal Year: 2005
    ..Thus, development of this unique resource will be of use to investigators supported by multiple NIH Institutes and Centers including NIDDK, NIAID, NCI, and NIGMS. ..