Cutting edge: A transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway.
IL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on proinflammatory mediator production. In this study we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3, and a helicase family corepressor, Strawberry notch homologue 2 (SBNO2), in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3 and a stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway regulated by IL-10 but not by STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 repressed NF-kappaB- but not IFN regulatory factor 7 (IRF7)-activated transcriptional reporters. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10.
El Kasmi
Karim C
KC
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Smith
Amber M
AM
Williams
Lynn
L
Neale
Geoffrey
G
Panopoulos
Athanasia D
AD
Panopolous
Athanasia
A
Watowich
Stephanie S
SS
Häcker
Hans
H
Foxwell
Brian M J
BM
Murray
Peter J
PJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050783:Proto-Oncogene Proteins c-ets / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C088164:ETV3 protein, human; C412319:ETV3 protein, mouse; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C526191:SBNO2 protein, human; C526192:SBNO2 protein, mouse; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D014157:Transcription Factors; D016753:Interleukin-10