Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon.
Interleukin-10 (IL-10) selectively inhibited lipopolysaccharide (LPS)-induced chemoattractant cytokine gene expression: levels of IP-10 mRNA were markedly suppressed in IL-10-treated mouse peritoneal macrophages, whereas the expression of the RANTES mRNA was only modestly reduced. IL-10 inhibited IP-10 mRNA accumulation by reducing IP-10 gene transcription as demonstrated by nuclear run-on analysis. Interestingly, the ability of IL-10 to inhibit expression of IP-10 was dependent on the inducing stimulus; IL-10 did not suppress interferon gamma (IFNgamma)- or IFNbeta-stimulated IP-10 transcription or mRNA accumulation. These results suggested that IL-10 might act indirectly to suppress IP-10 expression by inhibiting LPS-induced class I IFN production. This hypothesis was supported by the following observations. First, LPS-induced IP-10 mRNA expression was blocked in cells cotreated with cycloheximide. Second, IL-10 inhibited the production of IFN/beta-mediated antiviral activity. Finally, the IL-10-mediated suppression of LPS-stimulated IP-10 production could be rescued by cotreatment with IFNbeta.
Tebo
J M
JM
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Kim
H S
HS
Gao
J
J
Armstrong
D A
DA
Hamilton
T A
TA
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007370:Interferon Type I / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D007370:Interferon Type I; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D016899:Interferon-beta; D007371:Interferon-gamma; D003513:Cycloheximide