Interleukin-10 inhibits lipopolysaccharide induced miR-155 precursor stability and maturation.
The anti-inflammatory cytokine interleukin-10 (IL-10) is essential for attenuating the inflammatory response, which includes reducing the expression of pro-inflammatory microRNA-155 (miR-155) in lipopolysaccharide (LPS) activated macrophages. miR-155 enhances the expression of pro-inflammatory cytokines such as TNFα and suppresses expression of anti-inflammatory molecules such as SOCS1. Therefore, we examined the mechanism by which IL-10 inhibits miR-155. We found that IL-10 treatment did not affect the transcription of the miR-155 host gene nor the nuclear export of pre-miR-155, but rather destabilized both pri-miR-155 and pre-miR-155 transcripts, as well as interfered with the final maturation of miR-155. This inhibitory effect of IL-10 on miR-155 expression involved the contribution of both the STAT3 transcription factor and the phosphoinositol phosphatase SHIP1. This is the first report showing evidence that IL-10 regulates miRNA expression post-transcriptionally.
Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
Sylvia T
ST
Cheung
Eva Y
EY
So
David
D
Chang
Andrew
A
Ming-Lum
Alice L-F
AL
Mui
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000072181:Inositol Polyphosphate 5-Phosphatases; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D020871:RNA Stability / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D008070:Lipopolysaccharides; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012322:RNA Precursors; D050796:STAT3 Transcription Factor; D016753:Interleukin-10; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases