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Gene Review

Ifnb1  -  interferon beta 1, fibroblast

Mus musculus

Synonyms: IFN-beta, IFNB, Ifb, Ifnb, Interferon beta
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Disease relevance of Ifnb1


Psychiatry related information on Ifnb1

  • None of the mouse IFNs tested (IFN-alpha/beta, IFN-beta, and IFN-gamma, 3 x 10(5) U/kg, i.v.) changed the immobility time or the spontaneous locomotor activity in mice [5].

High impact information on Ifnb1

  • Evidence has been provided that a mouse nuclear factor, termed interferon regulatory factor-1 (IRF-1), specifically binds to the upstream regulatory region of the human IFN-beta gene and mediates virus-induced transcription of the gene [6].
  • This IFN-beta gene induction mechanism is distinct from that induced by virus, and is dependent on c-Fos itself [1].
  • They furthermore initiate the production of IFN-gamma, IFN-alpha, IFN-beta, and interleukins 12 and 18, all of which foster Th1 responses and enhance cell-mediated immunity [7].
  • Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1 [8].
  • The expression of HPV16 E6 in primary human keratinocytes inhibits the induction of IFNbeta mRNA following Sendai virus infection [9].

Chemical compound and disease context of Ifnb1


Biological context of Ifnb1

  • HMG I(Y) specifically interacts with the basic-leucine zipper region of ATF-2(195), and HMG I(Y) binds to two sites immediately flanking the ATF-2 binding site of the IFN-beta promoter [15].
  • We have recently demonstrated that TLR2 agonists poorly induce a subset of TLR4-inducible proinflammatory genes (e.g., inducible protein (IP)-10, inducible NO synthase (iNOS), monocyte chemoattractant protein-5, IL-12p40), due in part to differential activation of IFN-beta production and phosphorylation of the transcription factor STAT1 [16].
  • Neutralizing Ab against IFN-beta attenuated TLR4-mediated microglial apoptosis [17].
  • In humans, however, IFN-beta-induced up-regulation of TLR3 was blocked by pretreatment with LPS, despite the efficient induction of IRF-1 [18].
  • IFN-beta alone, however, did not induce a significant cell death [17].

Anatomical context of Ifnb1

  • Basal and LPS-induced expression of IFN-beta and IFN-alpha4 mRNA in Tyk2-null macrophages were diminished [19].
  • Low IFN-alpha or IFN-beta doses (500-10(3) U/mouse) down-modulate CD8(+) T cells priming in vivo [20].
  • The results also show that an NK clone, when stimulated with Sendai virus, produced a type 1 IFN (IFN alpha and/or IFN beta), suggesting that murine NK cells can produce both type 1 (alpha and/or beta) and type 2 (gamma) IFN, depending on inducers [21].
  • IFN-gamma and IFN-beta independently stimulate the expression of lipopolysaccharide-inducible genes in murine peritoneal macrophages [22].
  • We suggest that lack of endogenous IFN-beta in CNS leads to augmented microglia activation, resulting in a sustained inflammation, cytokine production, and tissue damage with consequent chronic neurological deficits [4].

Associations of Ifnb1 with chemical compounds

  • Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-beta (IFN-beta) in a MyD88-independent manner [19].
  • Moreover, IFN-alpha or IFN-beta in combination with LPS could also induce NO2- production in macrophages, as was previously reported for IFN-gamma plus LPS [23].
  • The treatment of PM with L-arginine-N(G)-amine (AA), a potent inhibitor of NO-producing enzymes, resulted in a marked accumulation of IFN-alpha4 mRNA and, to a minor extent, of IFN-beta mRNA [24].
  • Our results show that the injection of polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, into the striatum of the mouse brain induces the activation of astrocytes and the expression of TNF-alpha, IFN-beta, and IP-10 [25].
  • In the presence of cycloheximide, virally induced IFN-beta gene expression of C-76 cells was suppressed, whereas R1 and R2 cells produced IFN-beta 7.5- and 2.2-fold higher than C-76 cells respectively [26].

Physical interactions of Ifnb1

  • We show that YY1 specifically binds in vitro and in vivo to the murine IFN-beta promoter at positions -90 and -122 [27].

Regulatory relationships of Ifnb1


Other interactions of Ifnb1


Analytical, diagnostic and therapeutic context of Ifnb1


  1. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H., Suzuki, T., Sato, K., Yokochi, T., Oda, H., Nakamura, K., Ida, N., Wagner, E.F., Taniguchi, T. Nature (2002) [Pubmed]
  2. Interferon beta, a cofactor in the interferon gamma production induced by gram-negative bacteria in mice. Yaegashi, Y., Nielsen, P., Sing, A., Galanos, C., Freudenberg, M.A. J. Exp. Med. (1995) [Pubmed]
  3. In vivo interferon regulatory factor 3 tumor suppressor activity in B16 melanoma tumors. Duguay, D., Mercier, F., Stagg, J., Martineau, D., Bramson, J., Servant, M., Lin, R., Galipeau, J., Hiscott, J. Cancer Res. (2002) [Pubmed]
  4. IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis. Teige, I., Treschow, A., Teige, A., Mattsson, R., Navikas, V., Leanderson, T., Holmdahl, R., Issazadeh-Navikas, S. J. Immunol. (2003) [Pubmed]
  5. Human interferon-alpha induces immobility in the mouse forced swimming test: involvement of the opioid system. Makino, M., Kitano, Y., Komiyama, C., Hirohashi, M., Kohno, M., Moriyama, M., Takasuna, K. Brain Res. (2000) [Pubmed]
  6. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Miyamoto, M., Fujita, T., Kimura, Y., Maruyama, M., Harada, H., Sudo, Y., Miyata, T., Taniguchi, T. Cell (1988) [Pubmed]
  7. Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Roman, M., Martin-Orozco, E., Goodman, J.S., Nguyen, M.D., Sato, Y., Ronaghy, A., Kornbluth, R.S., Richman, D.D., Carson, D.A., Raz, E. Nat. Med. (1997) [Pubmed]
  8. Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Fujita, T., Kimura, Y., Miyamoto, M., Barsoumian, E.L., Taniguchi, T. Nature (1989) [Pubmed]
  9. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Ronco, L.V., Karpova, A.Y., Vidal, M., Howley, P.M. Genes Dev. (1998) [Pubmed]
  10. Binding of Legionella pneumophila to macrophages increases cellular cytokine mRNA. Yamamoto, Y., Okubo, S., Klein, T.W., Onozaki, K., Saito, T., Friedman, H. Infect. Immun. (1994) [Pubmed]
  11. Production of interferon-beta by murine T-cell lines induced by 10-carboxymethyl-9-acridanone. Storch, E., Kirchner, H., Brehm, G., Hüller, K., Marcucci, F. Scand. J. Immunol. (1986) [Pubmed]
  12. TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages. Toshchakov, V., Jones, B.W., Perera, P.Y., Thomas, K., Cody, M.J., Zhang, S., Williams, B.R., Major, J., Hamilton, T.A., Fenton, M.J., Vogel, S.N. Nat. Immunol. (2002) [Pubmed]
  13. Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids. Wieland, S.F., Eustaquio, A., Whitten-Bauer, C., Boyd, B., Chisari, F.V. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-beta during acute ocular herpes simplex virus type 1 infection. Austin, B.A., James, C., Silverman, R.H., Carr, D.J. J. Immunol. (2005) [Pubmed]
  15. The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms. Du, W., Maniatis, T. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  16. Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages. Schilling, D., Thomas, K., Nixdorff, K., Vogel, S.N., Fenton, M.J. J. Immunol. (2002) [Pubmed]
  17. TLR4, but not TLR2, signals autoregulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker. Jung, D.Y., Lee, H., Jung, B.Y., Ock, J., Lee, M.S., Lee, W.H., Suk, K. J. Immunol. (2005) [Pubmed]
  18. Species-specific regulation of Toll-like receptor 3 genes in men and mice. Heinz, S., Haehnel, V., Karaghiosoff, M., Schwarzfischer, L., Müller, M., Krause, S.W., Rehli, M. J. Biol. Chem. (2003) [Pubmed]
  19. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Karaghiosoff, M., Steinborn, R., Kovarik, P., Kriegshäuser, G., Baccarini, M., Donabauer, B., Reichart, U., Kolbe, T., Bogdan, C., Leanderson, T., Levy, D., Decker, T., Müller, M. Nat. Immunol. (2003) [Pubmed]
  20. Type I IFN negatively regulates CD8+ T cell responses through IL-10-producing CD4+ T regulatory 1 cells. Dikopoulos, N., Bertoletti, A., Kröger, A., Hauser, H., Schirmbeck, R., Reimann, J. J. Immunol. (2005) [Pubmed]
  21. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). II. IL 2-induced interferon gamma production. Handa, K., Suzuki, R., Matsui, H., Shimizu, Y., Kumagai, K. J. Immunol. (1983) [Pubmed]
  22. IFN-gamma and IFN-beta independently stimulate the expression of lipopolysaccharide-inducible genes in murine peritoneal macrophages. Hamilton, T.A., Bredon, N., Ohmori, Y., Tannenbaum, C.S. J. Immunol. (1989) [Pubmed]
  23. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. Ding, A.H., Nathan, C.F., Stuehr, D.J. J. Immunol. (1988) [Pubmed]
  24. Inhibitory activity of constitutive nitric oxide on the expression of alpha/beta interferon genes in murine peritoneal macrophages. Guillemard, E., Varano, B., Belardelli, F., Quero, A.M., Gessani, S. J. Virol. (1999) [Pubmed]
  25. TLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expression. Park, C., Lee, S., Cho, I.H., Lee, H.K., Kim, D., Choi, S.Y., Oh, S.B., Park, K., Kim, J.S., Lee, S.J. Glia (2006) [Pubmed]
  26. Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor-1 and -2. Park, K.C., Shimizu, K., Hayakawa, T., Tanaka, N. Br. J. Cancer (1998) [Pubmed]
  27. Transcription factor YY1 binds to the murine beta interferon promoter and regulates its transcriptional capacity with a dual activator/repressor role. Weill, L., Shestakova, E., Bonnefoy, E. J. Virol. (2003) [Pubmed]
  28. Induction of iNOS expression and antimicrobial activity by interferon (IFN)-beta is distinct from IFN-gamma in Burkholderia pseudomallei-infected mouse macrophages. Utaisincharoen, P., Anuntagool, N., Arjcharoen, S., Limposuwan, K., Chaisuriya, P., Sirisinha, S. Clin. Exp. Immunol. (2004) [Pubmed]
  29. Toll-like receptor 3 ligand-induced antiviral response in mouse osteoblastic cells. Nakamura, K., Deyama, Y., Yoshimura, Y., Suzuki, K., Morita, M. Int. J. Mol. Med. (2007) [Pubmed]
  30. Activation of Tyk2 and Stat3 is required for the apoptotic actions of interferon-beta in primary pro-B cells. Gamero, A.M., Potla, R., Wegrzyn, J., Szelag, M., Edling, A.E., Shimoda, K., Link, D.C., Dulak, J., Baker, D.P., Tanabe, Y., Grayson, J.M., Larner, A.C. J. Biol. Chem. (2006) [Pubmed]
  31. Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signaling. Freudenberg, M.A., Merlin, T., Kalis, C., Chvatchko, Y., Stübig, H., Galanos, C. J. Immunol. (2002) [Pubmed]
  32. Induction of macrophage nitric oxide production by Gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes. Mizel, S.B., Honko, A.N., Moors, M.A., Smith, P.S., West, A.P. J. Immunol. (2003) [Pubmed]
  33. Re-examination of the role of suppressor of cytokine signaling 1 (SOCS1) in the regulation of toll-like receptor signaling. Gingras, S., Parganas, E., de Pauw, A., Ihle, J.N., Murray, P.J. J. Biol. Chem. (2004) [Pubmed]
  34. Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide production by the cytokine-inducible pathway. Ma, Y., Seiler, K.P., Tai, K.F., Yang, L., Woods, M., Weis, J.J. Infect. Immun. (1994) [Pubmed]
  35. Mx1 and IP-10: Biomarkers to Measure IFN-beta Activity in Mice Following Gene-Based Delivery. Petry, H., Cashion, L., Szymanski, P., Ast, O., Orme, A., Gross, C., Bauzon, M., Brooks, A., Schaefer, C., Gibson, H., Qian, H., Rubanyi, G.M., Harkins, R.N. J. Interferon Cytokine Res. (2006) [Pubmed]
  36. Exogenous interferon-gamma induces endogenous synthesis of interferon-alpha and -beta by murine macrophages for induction of nitric oxide synthase. Zhou, A., Chen, Z., Rummage, J.A., Jiang, H., Kolosov, M., Kolosova, I., Stewart, C.A., Leu, R.W. J. Interferon Cytokine Res. (1995) [Pubmed]
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