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- W4313331142 endingPage "4744" @default.
- W4313331142 startingPage "4736" @default.
- W4313331142 abstract "Abstract Human IFN-γ-inducible protein, 10 kDa (hIP-10) and murine IP-10 (mIP-10) genes are induced by IFN-γ alone, and synergistically induced by TNF-α and IFN-γ. Upstream regions of the human and murine genes contain conserved regulatory motifs, including an IFN-stimulated response element (ISRE), which governs response of the mIP-10 gene to IFN-γ. Trans-acting factors mediating the IFN-γ response via ISRE remain incompletely defined. We examined ISRE-binding factors in the regulation of the hIP-10 gene. The requirement of p48 for hIP-10 induction by IFN-γ, with or without TNF-α, was demonstrated using p48-deficient U2A cells. An hIP-10 promoter-reporter mutant (mISRE3) that was relatively deficient for binding a related factor, IFN regulatory factor-1 (IRF-1) but competent for binding p48, was induced as well as the wild-type hIP-10 promoter, supporting the interpretation that p48 played a necessary and sufficient role in hIP-10 transcription. Genomic in vivo footprinting revealed IFN-γ/TNF-α-inducible binding at the ISRE consistent with the presence of p48 and associated factors, but not with IRF-1. Induction of hIP-10 by TNF-α/IFN-γ also required NFκB binding sites, which were protected in vivo and bound p65 homodimeric NFκB in vitro. These results documented the essential role of p48 (complexed with STAT-1α) for induction and sustained transcription of the IP-10 gene, strongly suggesting that IRF-1 is not required for IP-10 induction by these inflammatory cytokines." @default.
- W4313331142 created "2023-01-06" @default.
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- W4313331142 date "1998-11-01" @default.
- W4313331142 modified "2023-10-14" @default.
- W4313331142 title "p48/STAT-1α-Containing Complexes Play a Predominant Role in Induction of IFN-γ-Inducible Protein, 10 kDa (IP-10) by IFN-γ Alone or in Synergy with TNF-α" @default.
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- W4313331142 doi "https://doi.org/10.4049/jimmunol.161.9.4736" @default.
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