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- Title
Inducible MicroRNA-223 Down-Regulation Promotes TLR-Triggered IL-6 and IL- 1b Production in Macrophages by Targeting STAT3.
- Authors
Qingyun Chen; Hui Wang; Yang Liu; Yinjing Song; Lihua Lai; Quan Han; Xuetao Cao; Qingqing Wang; Viola, Joao P. B.
- Abstract
MicroRNAs are small non-coding RNA molecules that regulate gene expression by either translational inhibition or mRNA degradation. MicroRNAs play pivotal roles in the regulation of both innate and adaptive immune responses, including TLR-triggered inflammatory response. Here we reported that the expression of microRNA-223 (miR-223) was significantly decreased in murine macrophages during activation by lipopolysaccharide (LPS) or poly (I:C) stimulation. The inducible miR-223 down-regulation resulted in the activation of signal transducer and activator of transcription 3 (STAT3), which is directly targeted by miR-223, thus promoting the production of pro-inflammatory cytokines IL-6 and IL-1β, but not TNF-α. Interestingly, IL-6 was found to be a main factor in inducing the decrease in miR-223 expression after LPS stimulation, which formed a positive feedback loop to regulate IL-6 and IL-1β. Herein, our findings provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-6 production after TLR-triggered macrophage activation.
- Subjects
MICRORNA; NON-coding RNA; GENE expression; IMMUNE response; LIPOPOLYSACCHARIDES; CELLULAR signal transduction; CYTOKINES; MACROPHAGE activation
- Publication
PLoS ONE, 2012, Vol 7, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0042971