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 α7-nicotinic acetylcholine receptor （α7nAChR） on macrophages. However, the intracellular mechanisms that link a7nAChR activation and pro-inflammatory cytokine production rema...

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Published in:	Cell research Vol. 23; no. 11; pp. 1270 - 1283
Main Authors:	Sun, Yang, Li, Qi, Gui, Huan, Xu, Dong-Ping, Yang, Yi-Li, Su, Ding-Feng, Liu, Xia
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01.11.2013 Nature Publishing Group
Subjects:	631/250/127 631/250/2504/342 631/250/256 631/337/384/331 Acetylcholine receptors ADAM Proteins - metabolism ADAM17 Protein alpha7 Nicotinic Acetylcholine Receptor - metabolism Animals Biomedical and Life Sciences Cell Biology Cells, Cultured Cholinergic Neurons - metabolism Cytokines - biosynthesis Cytokines - genetics Cytokines - secretion HEK293 Cells Humans Interleukin-6 - biosynthesis Interleukin-6 - genetics Life Sciences Lipopolysaccharides - antagonists & inhibitors Lipopolysaccharides - pharmacology Macrophages - metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL MicroRNAs - metabolism Original original-article Sepsis - chemically induced Sepsis - genetics Sepsis - metabolism Sepsis - pathology siRNA STAT3 STAT3 Transcription Factor - metabolism TNF-α Transcription, Genetic Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics 乙酰胆碱受体介导抗炎作用细胞因子胆碱能 macrophages septic shock α7nAChR cholinergic anti-inflammatory action STAT3 TACE micorRNA-124
ISSN:	1001-0602, 1748-7838, 1748-7838
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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 a7nAChR 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-o 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.
AbstractList	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. 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 a7nAChR 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-o 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. 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. 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.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.
Author	Yang Sun Qi Li Huan Gui Dong-Ping Xu Yi-LiYang Ding-Feng Su Xia Liu
AuthorAffiliation	Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
Author_xml	– sequence: 1 givenname: Yang surname: Sun fullname: Sun, Yang organization: Department of Pharmacology, School of Pharmacy, Second Military Medical University – sequence: 2 givenname: Qi surname: Li fullname: Li, Qi organization: Department of Pharmacology, School of Pharmacy, Second Military Medical University – sequence: 3 givenname: Huan surname: Gui fullname: Gui, Huan organization: Department of Pharmacology, School of Pharmacy, Second Military Medical University – sequence: 4 givenname: Dong-Ping surname: Xu fullname: Xu, Dong-Ping organization: Department of Pharmacology, School of Pharmacy, Second Military Medical University – sequence: 5 givenname: Yi-Li surname: Yang fullname: Yang, Yi-Li email: yiliyang@mail.nih.gov organization: Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health – sequence: 6 givenname: Ding-Feng surname: Su fullname: Su, Ding-Feng email: dfsu2008@gmail.com organization: Department of Pharmacology, School of Pharmacy, Second Military Medical University – sequence: 7 givenname: Xia surname: Liu fullname: Liu, Xia email: lxflying@aliyun.com organization: Department of Pharmacology, School of Pharmacy, Second Military Medical University
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23979021$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Copyright	The Author(s) 2013 Copyright Nature Publishing Group Nov 2013 Copyright © 2013 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2013 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
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DocumentTitleAlternate	MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines miR-124 and the cholinergic anti-inflammation
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ISSN	1001-0602 1748-7838
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Keywords	macrophages septic shock α7nAChR cholinergic anti-inflammatory action STAT3 TACE micorRNA-124
Language	English
License	https://creativecommons.org/licenses/by-nc-nd/3.0 This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0
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Notes	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 a7nAChR 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-o 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. 31-1568/Q microRNA-124; cholinergic anti-inflammatory action; ct7nAChR; macrophages; septic shock; STAT3; TACE ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 These two authors contributed equally to this work.
OpenAccessLink	https://pubmed.ncbi.nlm.nih.gov/PMC3817544
PMID	23979021
PQID	1448240721
PQPubID	536307
PageCount	14
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_3817544 proquest_miscellaneous_1464503031 proquest_miscellaneous_1449282100 proquest_journals_1448240721 pubmed_primary_23979021 crossref_citationtrail_10_1038_cr_2013_116 crossref_primary_10_1038_cr_2013_116 springer_journals_10_1038_cr_2013_116 chongqing_primary_47769860
PublicationCentury	2000
PublicationDate	2013-11-01
PublicationDateYYYYMMDD	2013-11-01
PublicationDate_xml	– month: 11 year: 2013 text: 2013-11-01 day: 01
PublicationDecade	2010
PublicationPlace	London
PublicationPlace_xml	– name: London – name: England
PublicationTitle	Cell research
PublicationTitleAbbrev	Cell Res
PublicationTitleAlternate	Cell Research
PublicationYear	2013
Publisher	Nature Publishing Group UK Nature Publishing Group
Publisher_xml	– name: Nature Publishing Group UK – name: Nature Publishing Group
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Snippet	The vagus nerve can control inflammatory response through a ＇cholinergic anti-inflammatory pathway＇, which is mediated by the α7-nicotinic acetylcholine... The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the α7-nicotinic acetylcholine... The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the alpha 7-nicotinic acetylcholine...
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SubjectTerms	631/250/127 631/250/2504/342 631/250/256 631/337/384/331 Acetylcholine receptors ADAM Proteins - metabolism ADAM17 Protein alpha7 Nicotinic Acetylcholine Receptor - metabolism Animals Biomedical and Life Sciences Cell Biology Cells, Cultured Cholinergic Neurons - metabolism Cytokines - biosynthesis Cytokines - genetics Cytokines - secretion HEK293 Cells Humans Interleukin-6 - biosynthesis Interleukin-6 - genetics Life Sciences Lipopolysaccharides - antagonists & inhibitors Lipopolysaccharides - pharmacology Macrophages - metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL MicroRNAs - metabolism Original original-article Sepsis - chemically induced Sepsis - genetics Sepsis - metabolism Sepsis - pathology siRNA STAT3 STAT3 Transcription Factor - metabolism TNF-α Transcription, Genetic Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics 乙酰胆碱受体介导抗炎作用细胞因子胆碱能
Title	MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines
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