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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins / metabolism
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ADAM17 Protein
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Animals
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Cells, Cultured
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Cholinergic Neurons / metabolism*
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Cytokines / biosynthesis*
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Cytokines / genetics
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Cytokines / metabolism
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HEK293 Cells
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Humans
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Macrophages / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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MicroRNAs / metabolism*
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STAT3 Transcription Factor / metabolism
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Sepsis / chemically induced
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Sepsis / genetics
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Sepsis / metabolism
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Sepsis / pathology
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Transcription, Genetic
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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alpha7 Nicotinic Acetylcholine Receptor / metabolism
Substances
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Cytokines
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Interleukin-6
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Lipopolysaccharides
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MIRN124 microRNA, human
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MicroRNAs
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Mirn124 microRNA, mouse
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STAT3 Transcription Factor
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Tumor Necrosis Factor-alpha
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alpha7 Nicotinic Acetylcholine Receptor
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ADAM Proteins
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ADAM17 Protein
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ADAM17 protein, human
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Adam17 protein, mouse