title: Serum response factor indirectly regulates type I interferon-signaling in macrophages.
abstract: Serum response factor (SRF) is required for diverse aspects of development and homeostasis, but potential roles in the regulation of inflammation and immunity have not been systematically investigated. Here, we demonstrate that SRF is unexpectedly required for optimal responses of elicited peritoneal macrophages to type I interferons. Knockdown of SRF expression in these cells impairs induction of numerous interferon (IFN)-stimulated genes (ISGs) in response to zymosan, LPS, and poly I:C. This effect is primarily due to a defect in the ability of induced type I interferons to mediate secondary activation of ISGs. SRF does not appear to be required for expression of established components of the type I interferon signaling pathway, with IFN-β-dependent phosphorylation of STAT1 and STAT2 normally occurring in SRF-depleted macrophages. Collectively, these findings suggest that SRF can indirectly modulate type I interferon-signaling, without interfering with the classic JAK/STAT/ISGF3 pathway.
authors.affiliation: 1 Medical Systems Biology Research Center, School of Medicine, Tsinghua University , Beijing, China .
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sullivan
authors.forename: Jana G
authors.initials: JG
authors.lastname: Collier
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
mesh_terms: D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism*; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D059372:Nucleotide Motifs; D056510:Position-Specific Scoring Matrices; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D020871:RNA Stability; D050791:STAT Transcription Factors / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050791:STAT Transcription Factors; D026362:Serum Response Factor; D016899:Interferon-beta; D053612:Janus Kinases