Disease relevance of Irf1

• In C57BL/6 mice undergoing 60 min of hepatic ischemia, IRF-1 protein expression increased as early as 1 h after reperfusion [1].
• The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury [1].
• This IRF-1-dependent inhibition of iNOS activation might be partly responsible for the protective effect of MPA in EAE, prompting investigation of its potential use in multiple sclerosis [2].
• Retinoic acid and polyriboinosinic acid act synergistically to enhance the antibody response to tetanus toxoid during vitamin A deficiency: possible involvement of interleukin-2 receptor-beta, signal transducer and activator of transcription-1, and interferon regulatory factor-1 [3].
• We have identified IRF-1 expression in hepatocytes in vivo in sepsis [4].

High impact information on Irf1

• LPS, IL-6, or IFN-gamma induced a novel binding complex for GAS, which also existed in the 5'-flanking region of the IRF-1 gene [5].
• LPS or IL-6 increased binding complexes for the IRF site, which was compatible with induction of IRF-1 [5].
• Our studies show that the gene for IRF-1 is an immediate-early gene in Prl-stimulated T cells, which suggests that IRF-1 is a multifunctional molecule [6].
• In addition to its role in regulating growth-inhibitory interferon genes, IRF-1 may, therefore, also play a stimulatory role in cell proliferation [6].
• Surprisingly, DNA sequence analysis of c25 cDNA revealed that this Prl-inducible early-response gene is the rat homolog of the mouse transcription factor interferon-regulatory factor 1 (IRF-1), sharing 91% coding sequence similarity with mouse IRF-1 [6].

Chemical compound and disease context of Irf1

• In primary cultured rat brain astrocytes and C6 astroglioma cells, both cRA and tRA decreased IFN-gamma-induced expression of interferon regulatory factor-1 [7].

Biological context of Irf1

• Because IRF-1 contributed to liver injury, we also examined for inflammatory signals that regulated IRF-1 gene expression in cultured hepatocytes [1].
• Induction by TNF-alpha increased IRF-1 protein binding 3.5-fold, while binding levels of p53 protein increased six-fold [8].
• Protein/DNA array analysis revealed significant up-regulation of both IRF-1 and p53 protein in nuclear extracts [8].
• Using a 99-base pair segment of the iNOS gene promoter encompassing nucleotides -979 to -881, a region essential for gene activation by cytokines, we show that with increasing concentrations of added IRF-1, a monomeric then a dimeric complex form [9].
• Transcriptional activation of the gene is dependent on the interferon-gamma-induced transcription factor, interferon regulatory factor-1 (IRF-1) [9].

Anatomical context of Irf1

• There was no functional difference in the signal transducers and activators of transcription (STAT) pathways between progenitors and mature oligodendrocytes as determined by induction of IRF1 mRNA in response to IFNG [10].
• The suppression of the proinflammatory chemokine RANTES/CCL5 x 13cRA in fibroblasts could be mapped to a promoter module comprising IRF-1 and nuclear factor-kappaB binding elements, but direct binding of retinoid receptors to promoter elements could be excluded [11].
• Sequential binding of IRF-1 to form a dimeric complex has not been described previously, and we show that formation of this dimeric complex is essential for full activation of the iNOS gene by cytokines in vascular smooth muscle cells [9].
• The transcription factor interferon regulatory factor-1 is expressed during both early G1 and the G1/S transition in the prolactin-induced lymphocyte cell cycle [12].
• The observed MPA suppression of NO release and iNOS and IRF-1 induction in astrocytes were efficiently prevented by exogenous guanosine, indicating that the drug acted through reduction of IMPDH-dependent synthesis of guanosine nucleotides [2].

Associations of Irf1 with chemical compounds

• IL-6 and lipopolysaccharide had no effect on IRF-1 expression [1].
• Protein binding to the IRF-1 DNA element and IRF-1 gene activation by GH were not blunted by pretreatment with the protein synthesis inhibitor, cycloheximide, indicating that these hormonal effects are primary consequences of GH-activated signal transduction pathways [13].
• Ascorbate also attenuated the activation of transcription factor IRF-1 but not NF kappa B. These results indicate that ascorbate inhibits iNOS expression in ECs by an antioxidant mechanism independent of both NF kappa B activation and the reported negative feedback effect of nitric oxide [14].
• In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction [15].
• Among the three transcription factors, only IRF-1 and NFkappaB seemed to be involved in iNOS induction and its modulation by DETA and XO/X [16].

Regulatory relationships of Irf1

• Prolactin activates interferon regulatory factor-1 expression in normal lympho-hemopoietic cells [17].
• Growth hormone stimulates interferon regulatory factor-1 gene expression in the liver [13].
• Here we investigated whether strain-dependent, differential islet iNOS expression was associated with differences in islet expression of the IL-1 receptor type 1(IL-1RI) or interferon regulating factor 1 (IRF-1), and/or caused differences in HSP70 expression, a marker of cell defence against oxidative stress [18].
• Suppression of c-myc or fosB-induced cell transformation by the transcription factor IRF-1 [19].

Other interactions of Irf1

• This transcriptional regulation of IRF-1 gene by IFN-gamma and TNF-alpha was confirmed at the mRNA level [20].
• These data indicate that ethanol inhibits PRL-induced tyrosine phosphorylation of the JAK/STAT pathway resulting in decreased nuclear GAS DNA binding and inhibition of the PRL inducible gene, IRF-1 [21].
• The observed effect of taxol was mediated through induction of iNOS transcription factors NF-kappaB and IRF-1, and required the activation of p38 MAP kinase and JNK [22].
• Conversely, IFN-gamma, but not IL-1 beta, induced signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF)-1 binding [23].
• Expression of p53, c-fos, and the interferon regulatory factors IRF-1 and IRF-2, but not cdc2 or cdk, were also induced in mineralized bone nodules [24].

Analytical, diagnostic and therapeutic context of Irf1

• Western blot analysis revealed significant changes in immune modulator protein abundance in the obstructed versus sham-operated kidney for krox24 (P = 0.0004), IRF-1 (P = 0.005), MCP-1 (P = 0.01), and JunD (P = 0.0008) [25].
• The rise in IRF-1 transcripts was accompanied by induction of nuclear protein binding to a DNA element from the proximal IRF-1 promoter, as assessed by gel mobility shift assays; this element was shown previously to mediate PRL-activated gene transcription [13].
• Northern blot of hepatocyte RNA showed a single IRF-1 mRNA band at approximately 2.4 Kb [4].
• As shown after reverse transcription of mRNA by polymerase chain reaction, PRL, at physiological concentrations (0.01 microg/ml), stimulates the expression of the IRF-1 gene in these normal cells [17].
• Measurements: accumulated insulin and nitrite release into incubation medium, and islet mRNA and protein expression of iNOS, IL-1RI, IRF-1 and HSP70 by semi-quantitative RT-PCR and Western blotting [18].

References