IL-10 suppresses LPS-induced KC mRNA expression via a translation-dependent decrease in mRNA stability.
This study examines the mechanism of interleukin-10 (IL-10)-mediated suppression of KC chemokine gene expression in mouse macrophages. Suppression of KC mRNA levels by IL-10 occurred late in the time course of response to lipopolysaccharide (LPS). Equivalent IL-10-mediated suppression was observed when the agent was added 1 h before, simultaneous with, or 1 h after LPS. IL-10 did not inhibit KC gene transcription but rather produced a decrease in the stability of KC mRNA. The suppressive action of IL-10 was prevented in macrophages that were also treated with inhibitors of protein synthesis even when added 2 h after LPS and IL-10. These results suggest that IL-10 acts to destabilize LPS-induced KC mRNA through a process that depends on coincident KC mRNA translation.
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
H S
HS
Kim
D
D
Armstrong
T A
TA
Hamilton
J M
JM
Tebo
D000818:Animals; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D004347:Drug Interactions; D004355:Drug Stability; D015870:Gene Expression / Q000187:drug effects; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic / Q000187:drug effects
D019743:Chemokines, CXC; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10