title: miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway.
abstract: OBJECTIVE
  Although microRNA-132 (miR-132) has been shown to be involved in the inflammatory regulation, its role in sepsis-induced lung injury is unknown. We hypothesized that miR-132 attenuated lipopolysaccharide (LPS)-induced inflammation of alveolar macrophages by targeting acetylcholinesterase (AChE) and enhancing the acetylcholine (ACh)-mediated cholinergic anti-inflammatory response.
  
  
  METHODS
  The LPS-treated rat alveolar macrophage cell line NR8383 was used as the inflammatory model. To assess the effect of miR-132, alveolar macrophages were transfected with miR-132 mimic or inhibitor.
  
  
  RESULTS
  We found that miR-132 was upregulated in LPS-stimulated alveolar macrophages. Induction of AChE mRNA showed an inverse pattern with respect to AChE protein and activity, suggesting posttranscriptional regulation of AChE. Utilizing miR-132 mimic transfection, we found that overexpression of miR-132 enhanced the ACh-mediated cholinergic anti-inflammatory reaction by targeting AChE mRNA in LPS-treated alveolar macrophages. Blockage of miR-132 using miR-132 inhibitor reversed the Ach action upon LPS-induced release of inflammatory mediators and reduction in AchE protein/activity. Moreover, in the presence of ACh, upregulation of miR-132 suppressed LPS-induced nuclear translocation of NF-κB and production of STAT3 and phosphorylated STAT3, while downregulation of miR-132 enhanced the nuclear translocation of NF-κB.
  
  
  CONCLUSIONS
  We propose that miR-132 functions as a negative regulator of the inflammatory response in alveolar macrophages by potentiating the cholinergic anti-inflammatory pathway, and represents a potential therapeutic leverage point in modulating inflammatory responses.
authors.affiliation: 1Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi , China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Cheng
authors.initials: C
authors.lastname: Nie
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zeng
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.forename: Caixue
authors.initials: C
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Ding
authors.forename: Cheng
authors.initials: C
authors.lastname: Qing
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.forename: Erming
authors.initials: E
authors.lastname: Zeng
authors.forename: Kejian
authors.initials: K
authors.lastname: Qian
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018678:Cholinergic Agents / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018678:Cholinergic Agents; D008070:Lipopolysaccharides; C548821:MIRN132 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D000110:Acetylcholinesterase; D000109:Acetylcholine
keywords: NF-κB; STAT3; alveolar macrophage; cholinergic anti-inflammatory pathway; microRNA-132