Paun, AndreaReinert, Jorgen T.Jiang, ZhaozhaoMedin, Carey L.Balkhi, Mumtaz YaseenFitzgerald, Katherine APitha, Paula M.2022-08-232022-08-232008-03-122011-03-25J Biol Chem. 2008 May 23;283(21):14295-308. Epub 2008 Mar 10. <a href="http://dx.doi.org/10.1074/jbc.M800501200">Link to article on publisher's site</a>0021-9258 (Linking)10.1074/jbc.M80050120018332133https://hdl.handle.net/20.500.14038/35237Although the role of human IRF-5 in antiviral and inflammatory responses in vitro has been well characterized, much remains to be elucidated about murine IRF-5. Murine IRF-5, unlike the heavily spliced human gene, is primarily expressed as a full-length transcript, with only a single splice variant that was detected in very low levels in the bone marrow of C57BL/6J mice. This bone marrow variant contains a 288-nucleotide deletion from exons 4-6 and exhibits impaired transcriptional activity. The murine IRF-5 can be activated by both TBK1 and MyD88 to form homodimers and bind to and activate transcription of type I interferon and inflammatory cytokine genes. The importance of IRF-5 in the antiviral and inflammatory response in vivo is highlighted by marked reductions in serum levels of type I interferon and tumor necrosis factor alpha (TNFalpha) in Newcastle disease virus-infected Irf5(-)(/)(-) mice. IRF-5 is critical for TLR3-, TLR4-, and TLR9-dependent induction of TNFalpha in CD11c(+) dendritic cells. In contrast, TLR9, but not TLR3/4-mediated induction of type I IFN transcription, is dependent on IRF-5 in these cells. In addition, IRF-5 regulates TNFalpha but not type I interferon gene transcription in Newcastle disease virus-infected peritoneal macrophages. Altogether, these data reveal the cell type-specific importance of IRF-5 in MyD88-mediated antiviral pathways and the widespread role of IRF-5 in the regulation of inflammatory cytokines.en-USAlternative SplicingAmino Acid SequenceAnimalsCell LineConserved SequenceCytokinesDimerizationHumansInterferon Regulatory FactorsMiceMice, Inbred C57BLMolecular Sequence DataNewcastle DiseasePromoter Regions, GeneticProtein BindingSequence AlignmentToll-Like ReceptorsTranscription, GeneticImmunology and Infectious DiseaseJournal Articlehttps://escholarship.umassmed.edu/infdis_pp/711901393infdis_pp/71