title: MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines.
abstract: The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the α7-nicotinic acetylcholine receptor (α7nAChR) on macrophages. However, the intracellular mechanisms that link α7nAChR activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-α converting enzyme (TACE) to reduce TNF-α release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Yang
authors: Y
authors: Sun
authors: Qi
authors: Q
authors: Li
authors: Huan
authors: H
authors: Gui
authors: Dong-Ping
authors: DP
authors: Xu
authors: Yi-Li
authors: YL
authors: Yang
authors: Ding-Feng
authors: DF
authors: Su
authors: Xia
authors: X
authors: Liu
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D002478:Cells, Cultured; D059329:Cholinergic Neurons / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D018805:Sepsis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse
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