MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines

The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR) on macrophages. However, the intracellular mechanisms that link alpha 7nAChR 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-alpha converting enzyme (TACE) to reduce TNF-alpha release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.