Genomes and Genes
Gene Symbol: Il1a
Description: interleukin 1 alpha
Alias: Il-1a, interleukin-1 alpha, IL-1 alpha
- Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov E, et al. IL-1? and IL-1? recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol. 2011;187:4835-43 pubmed publisher..Overall, our data provide new insight into the biology of IL-1 molecules as well as on the regulation of sterile inflammation. ..
- Nambu A, Nakae S, Iwakura Y. IL-1beta, but not IL-1alpha, is required for antigen-specific T cell activation and the induction of local inflammation in the delayed-type hypersensitivity responses. Int Immunol. 2006;18:701-12 pubmed..In addition, CD4+ T cell-derived IL-1 plays an important role in the activation of DCs during the elicitation phase, resulting in the production of TNF, that activate allergen-specific T cells. ..
- Miller L, Pietras E, Uricchio L, Hirano K, Rao S, Lin H, et al. Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. J Immunol. 2007;179:6933-42 pubmed..aureus in vivo. ..
- Di Paolo N, Miao E, Iwakura Y, Murali Krishna K, Aderem A, Flavell R, et al. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity. 2009;31:110-21 pubmed publisher..Thus, these data identify IL-1 alpha-IL-1RI as a key pathway allowing for the activation of proinflammatory responses to the virus, independently of its genomic nucleic acid recognition. ..
- Lomedico P, Gubler U, Hellmann C, Dukovich M, Giri J, Pan Y, et al. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature. 1984;312:458-62 pubmed..The IL-1 cDNA codes for a polypeptide precursor of 270 amino acids. Biologically active IL-1 was produced in E. coli by expressing the carboxy-terminal 156 amino acids of the IL-1 precursor. ..
- Elkabets M, Krelin Y, Dotan S, Cerwenka A, Porgador A, Lichtenstein R, et al. Host-derived interleukin-1alpha is important in determining the immunogenicity of 3-methylcholantrene tumor cells. J Immunol. 2009;182:4874-81 pubmed publisher..Elucidation of the involvement of the IL-1 molecules in the malignant process will hopefully lead to the development of novel approaches for chemoprevention and immunotherapy. ..
- Clarke M, Talib S, Figg N, Bennett M. Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: effects of hyperlipidemia-mediated inhibition of phagocytosis. Circ Res. 2010;106:363-72 pubmed publisher..Thus, failed clearance of apoptotic VSMCs caused by hyperlipidemia in vivo may promote the increased serum cytokines and chronic inflammation associated with atherosclerosis. ..
- Nazarenko I, Marhaba R, Reich E, Voronov E, Vitacolonna M, Hildebrand D, et al. Tumorigenicity of IL-1alpha- and IL-1beta-deficient fibrosarcoma cells. Neoplasia. 2008;10:549-62 pubmed..Both sarcoma cell-derived IL-1alpha and IL-1beta promote tumor growth. However, IL-1alpha exerts regulatory activity on the tumor cell-matrix cross-talk, and only IL-1beta initiates systemic inflammation. ..
- Eigenbrod T, Park J, Harder J, Iwakura Y, Nunez G. Cutting edge: critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1 alpha released from dying cells. J Immunol. 2008;181:8194-8 pubmed..These studies show that IL-1alpha is a key danger signal released from necrotic cells to trigger CXCL1 secretion and recruitment of neutrophils via IL-1R/MyD88 on neighboring mesothelial cells. ..
- Kamari Y, Werman Venkert R, Shaish A, Werman A, Harari A, Gonen A, et al. Differential role and tissue specificity of interleukin-1alpha gene expression in atherogenesis and lipid metabolism. Atherosclerosis. 2007;195:31-8 pubmed..Furthermore, we showed that the expression of IL-1alpha in cells other than the bone marrow plays a significant role in non-HDL cholesterol metabolism. ..
- van Beelen A, Zelinkova Z, Taanman Kueter E, Muller F, Hommes D, Zaat S, et al. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity. 2007;27:660-9 pubmed..Thus, antibacterial Th17-mediated immunity in humans is orchestrated by DCs upon sensing bacterial NOD2-ligand MDP. ..
- Luheshi N, Rothwell N, Brough D. The dynamics and mechanisms of interleukin-1alpha and beta nuclear import. Traffic. 2009;10:16-25 pubmed publisher..These data provide valuable insights into the dynamic regulation of intracellular cytokine trafficking. ..
- Ortiz L, DuTreil M, Fattman C, Pandey A, Torres G, Go K, et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A. 2007;104:11002-7 pubmed..Identification of IL1RN-expressing human MSC subpopulations may provide a novel cellular vector for treating chronic inflammatory diseases in humans. ..
- Nakae S, Komiyama Y, Yokoyama H, Nambu A, Umeda M, Iwase M, et al. IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response. Int Immunol. 2003;15:483-90 pubmed..These observations indicate that IL-1 plays important roles in the development of AHR. ..
- Gross O, Yazdi A, Thomas C, Masin M, Heinz L, Guarda G, et al. Inflammasome activators induce interleukin-1? secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity. 2012;36:388-400 pubmed publisher..Because inflammasomes contribute to the pathology of numerous chronic inflammatory diseases such as gout and diabetes, IL-1? antagonists may be beneficial in the treatment of these disorders. ..
- Luheshi N, Kovacs K, Lopez Castejon G, Brough D, Denes A. Interleukin-1? expression precedes IL-1? after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues. J Neuroinflammation. 2011;8:186 pubmed publisher..This adds to the growing body of evidence that IL-1? is a key mediator of the sterile inflammatory response. ..
- Fettelschoss A, Kistowska M, LeibundGut Landmann S, Beer H, Johansen P, Senti G, et al. Inflammasome activation and IL-1? target IL-1? for secretion as opposed to surface expression. Proc Natl Acad Sci U S A. 2011;108:18055-60 pubmed publisher..We further demonstrate that IL-1? directly binds IL-1?, thus identifying IL-1? as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases. ..
- Barry K, Fontana M, Portman J, Dugan A, Vance R. IL-1? signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo. J Immunol. 2013;190:6329-39 pubmed publisher..Our results establish IL-1? as a critical initiator of the inflammatory response to L. pneumophila in vivo and point to an important role for IL-1? in providing an alternative to inflammasome-mediated immune responses in vivo. ..
- Nakae S, Asano M, Horai R, Iwakura Y. Interleukin-1 beta, but not interleukin-1 alpha, is required for T-cell-dependent antibody production. Immunology. 2001;104:402-9 pubmed..These results show that endogenous IL-1 beta, but not IL-1 alpha, is involved in T-cell-dependent antibody production, and IL-1 promotes the antigen-specific T-cell helper function through the T-cell-APC interaction. ..
- Kono H, Karmarkar D, Iwakura Y, Rock K. Identification of the cellular sensor that stimulates the inflammatory response to sterile cell death. J Immunol. 2010;184:4470-8 pubmed publisher..One key way they accomplish this important task is by producing IL-1alpha that is needed to initiate the inflammatory response...
- Zahedi K, Seldin M, Rits M, Ezekowitz R, Whitehead A. Mouse IL-1 receptor antagonist protein. Molecular characterization, gene mapping, and expression of mRNA in vitro and in vivo. J Immunol. 1991;146:4228-33 pubmed..Il 1rn gene was mapped to the proximal region of chromosome 2 between the centromere and Spna2; the other known members of the mouse IL-1 gene family, Il 1a and Il 1b, both map to the same chromosome, although not in close linkage.
- Silver A, Masson W, George A, Adam J, Cox R. The IL-1 alpha and beta genes are closely linked (less than 70 kb) on mouse chromosome 2. Somat Cell Mol Genet. 1990;16:549-56 pubmed..The apparent clustering of such hemopoietic genes is discussed in relation to evolutionary tandem gene duplication and possible associations with chromosomal fragile sites and leukemogenesis. ..
- D EUSTACHIO P, Jadidi S, Fuhlbrigge R, Gray P, Chaplin D. Interleukin-1 alpha and beta genes: linkage on chromosome 2 in the mouse. Immunogenetics. 1987;26:339-43 pubmed..7 centimorgans distal to B2m (beta-2 microglobulin). We have named the locus encoding IL-1 alpha Il-1 alpha and the locus encoding IL-1 beta Il-1b. ..
- Burysek L, Houstek J. Multifactorial induction of gene expression and nuclear localization of mouse interleukin 1 alpha. Cytokine. 1996;8:460-7 pubmed..The rapid responses of IL-1A gene expression to multifactorial stimulation and pronounced nuclear localization of IL-1 alpha proteins further support the existence of a hypothetical nuclear function of IL-1 alpha. ..
- Song X, Voronov E, Dvorkin T, Fima E, Cagnano E, Benharroch D, et al. Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness. J Immunol. 2003;171:6448-56 pubmed
- Cheng W, Shivshankar P, Zhong Y, Chen D, Li Z, Zhong G. Intracellular interleukin-1alpha mediates interleukin-8 production induced by Chlamydia trachomatis infection via a mechanism independent of type I interleukin-1 receptor. Infect Immun. 2008;76:942-51 pubmed..Thus, we have identified a novel mechanism for chlamydial induction of the chemokine IL-8. ..
- De M, Sanford T, Wood G. Detection of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in the uterus during the second half of pregnancy in the mouse. Endocrinology. 1992;131:14-20 pubmed..Those data showing the kinetics of cytokine production during fetal development raise the possibility that cytokines and cytokine-induced mediators modulate cellular events during the late stages of pregnancy in the mouse. ..
- Yamada H, Mizumo S, Horai R, Iwakura Y, Sugawara I. Protective role of interleukin-1 in mycobacterial infection in IL-1 alpha/beta double-knockout mice. Lab Invest. 2000;80:759-67 pubmed..Our data clearly indicate that IL-1 is important for the generation of early-phase protective immunity against mycobacterial infection. ..
- Zheng Y, Humphry M, Maguire J, Bennett M, Clarke M. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1?, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285-95 pubmed publisher..Thus, we report a cell type-dependent process that fundamentally governs IL-1? activity postnecrosis and the mechanism allowing conditional release of this blockade. ..
- Horai R, Asano M, Sudo K, Kanuka H, Suzuki M, Nishihara M, et al. Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion. J Exp Med. 1998;187:1463-75 pubmed..The importance of IL-1ra both in normal physiology and under stress is also suggested. ..
- Kumar S, McDonnell P, Lehr R, Tierney L, Tzimas M, Griswold D, et al. Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem. 2000;275:10308-14 pubmed..This suggests that IL-1H1 may be involved in pathogenesis of immune mediated disease processes. The addition of four novel IL-1 homologues suggests that the IL-1 family is significantly larger than previously thought. ..
- Hata H, Sakaguchi N, Yoshitomi H, Iwakura Y, Sekikawa K, Azuma Y, et al. Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J Clin Invest. 2004;114:582-8 pubmed..The results also indicate that targeting not only each cytokine but also each cell population secreting distinct cytokines could be an effective treatment of rheumatoid arthritis. ..
- Cohen I, Rider P, Carmi Y, Braiman A, Dotan S, White M, et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci U S A. 2010;107:2574-9 pubmed publisher..Tissues surrounding the necrotic site also sustain damage from the myeloid cells. Nuclear trafficking and differential release during necrosis vs. apoptosis demonstrate that inflammation by IL-1alpha is tightly controlled. ..
- Hurgin V, Novick D, Werman A, Dinarello C, Rubinstein M. Antiviral and immunoregulatory activities of IFN-gamma depend on constitutively expressed IL-1alpha. Proc Natl Acad Sci U S A. 2007;104:5044-9 pubmed..Furthermore, IFN-gamma induced serum IL-18 binding protein in wild-type mice but not in IL-1alpha/beta double-deficient mice. Thus, constitutively expressed IL-1alpha is critical for numerous IFN-gamma activities. ..
- Sakurai T, He G, Matsuzawa A, Yu G, Maeda S, Hardiman G, et al. Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell. 2008;14:156-65 pubmed publisher..IL-1 alpha release by necrotic hepatocytes is therefore an important mediator of liver tumorigenesis. ..
- Boutin H, LeFeuvre R, Horai R, Asano M, Iwakura Y, Rothwell N. Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci. 2001;21:5528-34 pubmed
- Almog T, Kandel Kfir M, Shaish A, Dissen M, Shlomai G, Voronov E, et al. Knockdown of interleukin-1Î± does not attenuate LPS-induced production of interleukin-1Î² in mouse macrophages. Cytokine. 2015;73:138-43 pubmed publisher..Rather, they suggest that IL-1Î± acts mainly as an alarmin that is sequestered in the nucleus following stimulation with TLR-4. ..
- Lane J, Neumann D, Lafond Walker A, Herskowitz A, Rose N. Interleukin 1 or tumor necrosis factor can promote Coxsackie B3-induced myocarditis in resistant B10.A mice. J Exp Med. 1992;175:1123-9 pubmed..Treatment with IL-1 or TNF alone promoted CB3-induced autoimmune myocarditis in resistant B10.A mice. Myocarditis was also observed when uninfected mice were immunized with syngeneic heart extract in the presence of IL-1 or TNF. ..
- Rogers H, Sheehan K, Brunt L, Dower S, Unanue E, Schreiber R. Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice. Proc Natl Acad Sci U S A. 1992;89:1011-5 pubmed..Using monoclonal antibodies that neutralize the biologic activities of interleukin 1 alpha and interleukin 1 beta, we document that interleukin 1 participates neither directly in the induction of ..
- De M, Sanford T, Wood G. Interleukin-1, interleukin-6, and tumor necrosis factor alpha are produced in the mouse uterus during the estrous cycle and are induced by estrogen and progesterone. Dev Biol. 1992;151:297-305 pubmed
- Oberyszyn T, Sabourin C, Bijur G, Oberyszyn A, Boros L, Robertson F. Interleukin-1 alpha gene expression and localization of interleukin-1 alpha protein during tumor promotion. Mol Carcinog. 1993;7:238-48 pubmed
- Wen P, Warden C, Fletcher B, Kujubu D, Herschman H, Lusis A. Chromosomal organization of the inducible and constitutive prostaglandin synthase/cyclooxygenase genes in mouse. Genomics. 1993;15:458-60 pubmed
- Brown D, Donaldson K, Stone V. Effects of PM10 in human peripheral blood monocytes and J774 macrophages. Respir Res. 2004;5:29 pubmed..Impaired motility and phagocytic ability as shown by changes in the F-actin cytoskeleton is likely to play a key role in particle clearance from the lung. ..
- Kuroishi T, Kinbara M, Sato N, Tanaka Y, Nagai Y, Iwakura Y, et al. Biotin status affects nickel allergy via regulation of interleukin-1beta production in mice. J Nutr. 2009;139:1031-6 pubmed publisher..These results indicate that biotin status affects Ni allergy in the elicitation phase via the upregulation of IL-1beta production in mice, suggesting that biotin supplementation may have therapeutic effects on human metal allergy. ..
- Oh Y, Na E, Gye M. Effects of bilateral vasectomy on the interleukin 1 system in mouse epididymis. Am J Reprod Immunol. 2016;76:235-42 pubmed publisher..Following VAX, IL1Î±, IL1Î², IL1ra, IL10, and TNF-Î± may mediate immune reaction in whole epididymis, whereas IL6 and TGF-Î²1 may mediate regionally different immune response primarily in the lower part of epididymis. ..
- Manils J, Casas E, Vina Vilaseca A, López Cano M, Díez Villanueva A, Gómez D, et al. The Exonuclease Trex2 Shapes Psoriatic Phenotype. J Invest Dermatol. 2016;136:2345-2355 pubmed publisher..Hence, our data indicate that Trex2 acts as a critical factor in the pathogenesis of psoriasis by promoting keratinocyte apoptosis and enucleation and thereby influencing skin immune responses. ..
- Lock L, Wickramasinghe D, Ernst M, Gilbert D, Copeland N, Jenkins N, et al. The Cdc25 genes map to mouse chromosomes 2, 9, and 18. Mamm Genome. 1996;7:771-2 pubmed
- Oboki K, Ohno T, Kajiwara N, Arae K, Morita H, Ishii A, et al. IL-33 is a crucial amplifier of innate rather than acquired immunity. Proc Natl Acad Sci U S A. 2010;107:18581-6 pubmed publisher..These observations indicate that IL-33 is a crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses. ..
- Cao Y, Jia S, Chakravarty G, de Crombrugghe B, Kleinerman E. The osterix transcription factor down-regulates interleukin-1 alpha expression in mouse osteosarcoma cells. Mol Cancer Res. 2008;6:119-26 pubmed publisher..These data suggest that Osx down-regulates IL-1alpha expression in mouse osteosarcoma cells via transcriptional repression of IL-1alpha and this may in turn affect the lytic activity of the tumor cells. ..
- Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci U S A. 2005;102:1906-10 pubmed..IL-1 may play a significant role in the anemia of inflammation by up-regulating hepcidin. ..
- Jiang Y, Lu B, Crumrine D, Man M, Elias P, Feingold K. IL-1alpha accelerates stratum corneum formation and improves permeability barrier homeostasis during murine fetal development. J Dermatol Sci. 2009;54:88-98 pubmed publisher..IL-1 plays a role in regulating the late stages of SC formation and permeability barrier ontogenesis. ..
- Lee S, Kalinowski J, Jastrzebski S, Lorenzo J. 1,25(OH)2 vitamin D3-stimulated osteoclast formation in spleen-osteoblast cocultures is mediated in part by enhanced IL-1 alpha and receptor activator of NF-kappa B ligand production in osteoblasts. J Immunol. 2002;169:2374-80 pubmed..These results demonstrate interactions between IL-1 and Vit D in primary osteoblasts that appear important in both regulation of IL-1alpha production and the ability of Vit D to support osteoclastogenesis. ..
- Trebec Reynolds D, Voronov I, Heersche J, Manolson M. IL-1alpha and IL-1beta have different effects on formation and activity of large osteoclasts. J Cell Biochem. 2010;109:975-82 pubmed publisher..These results demonstrate that IL-1 predominantly affects large OCs. The dissimilarity of responses to IL-1alpha and IL-1beta suggests that these isoforms activate different signaling pathways within the two OC populations. ..
- Lin D, Lei L, Zhang Y, Hu B, Bao G, Liu Y, et al. Secreted IL-1Î± promotes T-cell activation and expansion of CD11b(+) Gr1(+) cells in carbon tetrachloride-induced liver injury in mice. Eur J Immunol. 2015;45:2084-98 pubmed publisher..The controlled release of IL-1Î± could be a critical regulator during acute liver inflammation. ..
- Brikos C, Wait R, Begum S, O Neill L, Saklatvala J. Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components. Mol Cell Proteomics. 2007;6:1551-9 pubmed..The only component of the IL-1RI signaling complex that dissociated is IRAK-1. Our study is therefore the first detailed description of the endogenous IL-1RI complex. ..
- DeChiara T, Young D, Semionow R, Stern A, Batula Bernardo C, Fiedler Nagy C, et al. Structure-function analysis of murine interleukin 1: biologically active polypeptides are at least 127 amino acids long and are derived from the carboxyl terminus of a 270-amino acid precursor. Proc Natl Acad Sci U S A. 1986;83:8303-7 pubmed..This amino-terminal end flexibility supports a processing model for IL-1 maturation that partially explains IL-1 polypeptide heterogeneity. ..
- Di Paolo N, Shayakhmetov D. Interleukin 1? and the inflammatory process. Nat Immunol. 2016;17:906-13 pubmed publisher..In this review we examine key aspects of IL-1? biology and regulation and discuss its emerging importance in the initiation and maintenance of inflammation that underlie the pathology of many human diseases. ..
- Blumenfeld I, Livne E. The role of transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-1, and interleukin (IL)-1 in osteoarthritis and aging of joints. Exp Gerontol. 1999;34:821-9 pubmed
- Chang N, Jenkins N, Gilbert D, Copeland N, Chang Y, Chen W, et al. Assignment of two alpha 2 adrenoceptor subtype genes to murine chromosomes. Neurosci Lett. 1994;167:105-8 pubmed..Both genes mapped in regions of mouse chromosomes consistent with their map location in humans. These mapping results provide additional insights into the linkage relationships among members of this important gene family. ..