IL-10 inhibits miR-155 induction by toll-like receptors.
IL-10 is a potent anti-inflammatory cytokine that is crucial for down-regulating pro-inflammatory genes, which are induced by Toll-like receptor (TLR) signaling. In this study, we have examined whether modulation of microRNAs plays a role in the inhibitory effect of IL-10 on TLR4 signaling. Analyzing microRNAs known to be induced by TLR4, we found that IL-10 could inhibit the expression of miR-155 in response to lipopolysaccharide but had no effect on miR-21 or miR-146a. IL-10 inhibited miR-155 transcription from the BIC gene in a STAT3-dependent manner. This inhibitory effect of IL-10 on miR-155 led to an increase in the expression of the miR-155 target, SHIP1. This is the first example of IL-10 playing a role in microRNA function and suggests that through its inhibitory effect on miR-155, IL-10 has the ability to promote anti-inflammatory gene expression.
McCoy
Claire E
CE
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. cmccoy@tcd.ie
Sheedy
Frederick J
FJ
Qualls
Joseph E
JE
Doyle
Sarah L
SL
Quinn
Susan R
SR
Murray
Peter J
PJ
O'Neill
Luke A J
LA
D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D017930:Genes, Reporter; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007700:Kinetics; D008156:Luciferases / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D018076:DNA, Complementary; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D008156:Luciferases