title: Inducible microRNA-223 down-regulation promotes TLR-triggered IL-6 and IL-1β production in macrophages by targeting STAT3.
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.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yinjing
authors.initials: Y
authors.lastname: Song
authors.forename: Lihua
authors.initials: L
authors.lastname: Lai
authors.forename: Quan
authors.initials: Q
authors.lastname: Han
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C