Disease relevance of Ifnb1

• When the cultured cells of rat glioma cell line T9 were transfected with the plasmid, their growth was markedly suppressed due to the expression of rat IFN beta [1].
• Interferon-beta (IFN-beta), a substance clinically used in the treatment of the relapsing-remitting form of multiple sclerosis, was shown to inhibit the phagocytosis-induced upregulation of MHC-class II [2].
• Interferon-beta (IFN-beta) modestly reduces the frequency of relapses in MS and may have a small effect on the accumulation of permanent disability [3].
• Although important species differences exist in these glial responses this previously unrecognised property of IFN-beta may have implications for reducing astrocytosis and thereby promoting endogenous repair [3].
• The immunomodulatory cytokine interferon-beta (IFN-beta) is used in the treatment of autoimmune diseases such as multiple sclerosis [4].

High impact information on Ifnb1

• Taken together, these data suggest that a HDI inhibits osteoclastogenesis and bone destruction by a novel action to induce the expression of osteoclast inhibitory protein, IFN-beta [5].
• Inhibition of histone deacetylase suppresses osteoclastogenesis and bone destruction by inducing IFN-beta production [5].
• In this study, we show that a depsipeptide, FR901228, inhibited osteoclast differentiation by not only suppressing RANKL-induced nuclear translocation of NFATc1 but also increasing the mRNA level of IFN-beta, an inhibitor of osteoclastogenesis [5].
• We further revealed that activation of PKR by LPS led to the induction of IFN-beta through activation of NF-kappaB, triggering the phosphorylation of STAT1 in rat brain glial cells [6].
• Treatment of hepatocytes with 25-100 mM ethanol for 30 min inhibited IFN-beta- or IFN-gamma-induced STAT1 activation and tyrosine phosphorylation [7].

Chemical compound and disease context of Ifnb1

• In view of treatment of MS relapses, the synergistic effects in this study corroborate the use of a combination therapy with high-dose MP and IFN-beta [8].

Biological context of Ifnb1

• Rat interferon beta (IFN beta) was cloned from a part of rat genomic DNA by the polymerase chain reaction (PCR) with reference to the nucleotide sequence data of a mouse IFN beta [1].
• Our study indicates that IFN-beta affects the immunopathological process in EAE in several ways, but apoptosis appears as a minor component [8].
• Second, IFN-beta enhanced the rate of action potential firing [4].
• We propose that the beneficial effects of IFN-beta in MS therapy may depend, at least in part, on its capacity to protect astrocytes against the apoptotic cell death that occurs in the early steps of the pathogenesis of MS [9].
• LPS induced IFN-beta and IRF-1 gene expression were markedly suppressed by KE-758 [10].

Anatomical context of Ifnb1

• From the results of reverse transcription-PCR and cytopathic activity assay, this ORF expressed IFN beta in COS-1 cells [1].
• In subsequent experiments, the abilities of interferon beta (IFN beta), tumor necrosis factor alpha (TNF alpha), prostaglandin E2 (PGE2), and transforming growth factor beta (TFG beta), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFN gamma or CP, were compared [11].
• In the present work, we have found that IFN-beta treatment promotes the survival of astrocytes through stimulation of the phosphatidylinositol 3-kinase (PI-3K)/Akt pathway [9].
• IFN-beta tended to decrease T cell infiltration (46.1 +/- 12.7 cells/mm2) compared to controls (59.2 +/- 18.5 cells/mm2) [8].
• These data indicate that IFN-beta exerts direct antiinflammatory effects on brain endothelial cells thereby contributing to reduced lesion formation as observed in MS patients [12].

Associations of Ifnb1 with chemical compounds

• The inhibition of osteoclast formation by FR901228 was abrogated by the addition of IFN-beta-neutralizing Ab [5].
• In showing that IFN beta and TNF alpha were mostly enhancing and TGF beta mostly suppressive, whereas PGE2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage-derived molecules have a key role in autocrine regulation of macrophage functional activities [11].
• BBB disruption was ameliorated after IFN-beta but significantly only in combination with MP [8].
• However, the membrane response to IFN-beta in the subthreshold range was prevented by ZD7288 (a specific blocker of I(h)) but not by Ni2+, carbachol, or bicuculline, pointing to a dependence on an intact I(h) [4].
• In contrast, COP-1, the phosphodiesterase inhibitors rolipram and pentoxifylline, the cytokines interleukin-10 (IL-10) and interferon-beta (IFN-beta) as well as the steroids beta-estradiol, testosterone, and dehydroepiandrosterone (DHEA) showed no inhibitory effect [13].

Regulatory relationships of Ifnb1

• Our results show that both IFN-gamma and IFN-beta can induce a state of antiviral resistance in neural cells whereas TNF-alpha is effective only in astrocytes at low m.o.i.; they suggest an antiviral role of cytokines in the immune response to virus infections of the CNS [14].
• CONCLUSION: KE-758 suppressed LPS induced iNOS gene expression by murine macrophage cells by inhibiting IFN-beta/IRF-1 expression [10].
• IFN beta stimulates class I weakly and induced class II in one experiment but the effects seen when IFN gamma and IFN beta were used together were additive, not synergistic [15].

Other interactions of Ifnb1

• IFN-beta treatment resulted in a marked reduction of perivascular infiltrates in acute experimental allergic encephalomyelitis (EAE), the rat model for MS, which was coupled to a major decrease in the expression of the adhesion molecules ICAM-1 and VCAM-1 on brain capillaries [12].
• Matrix metalloproteinases (MMPs) have been identified as mediators of brain injury in multiple sclerosis (MS) and it has recently been reported that treatment of MS patients with interferon-beta (IFN-beta) reduces MMP-9 serum levels and in vitro release from monocytes [16].
• In diseased rats a five-fold increase in intraglomerular macrophages was found, but we could not detect intraglomerular IFN-alpha, IFN-beta, IL-1 beta or tumour necrosis factor-alpha (TNF-alpha) by using immunohistology [17].
• Also, TNF-alpha expression in macrophages was significantly reduced by IFN-beta and by the combination therapy [8].
• In contrast, MIF was expressed at the same level in neoplasms and normal tissue and no expression of IFNbeta, IFNgamma and GM-CSF was apparent in either adenocarcinomas or normal lung tissues [18].

Analytical, diagnostic and therapeutic context of Ifnb1

• Animals were treated with 3 x 10(5) units of recombinant rat IFN-beta s.c. once at 18 hr, or with 10 mg/kg methylprednisolone (MP) i.v. twice at 18 and 6 hr prior to dissection, or with a combination of both [8].
• After treatment with IFN-beta, IFN-gamma, or both for 3 days, steady-state levels of Rho-123, incorporated into the hepatocytes, were measured to evaluate the P-gp activity [19].
• In the present study, we evaluated the effects of wild-type rat IFN-beta and its pegylated counterpart (PEG-IFN-beta) in a model of focal ischemia and reperfusion [20].

References