Document Detail


TNF-α-induced CXCL8 production by A549 cells: Involvement of the non-neuronal cholinergic system.
MedLine Citation:
PMID:  23142559     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation. We investigated this system's involvement in the control of cytokine production by the A549 human alveolar epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-α increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R). Furthermore, TNF-α-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-α-induced CXCL8 secretion through activation of the M3R. Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-α-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of IκBα. Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release. Our results suggest that the TNF-α-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter's binding to the M3R and the downstream activation of NF-κB and the ERK1/2 and p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh.
Authors:
Z-P Xu; P Devillier; G-N Xu; L Zhu; W Zhou; L-N Hou; Y-B Tang; K Yang; Z-H Yu; H-Z Chen; Y-Y Cui
Related Documents :
24567099 - Methods for the study of caspase activation in the xenopus laevis oocyte and egg extract.
24035139 - Th17-mediated inflammation in asthma.
23955329 - Republished: novel insights into immune and inflammatory responses to respiratory viruses.
24876829 - Type 2 innate lymphoid cells in allergic disease.
24958469 - Antitumor effects in hepatocarcinoma of isoform-selective inhibition of hdac2.
24293629 - Tgf-β promotes immune responses in the presence of mesenchymal stem cells.
9329219 - Initiation of t-helper cell immunity to candida albicans by il-12: the role of neutroph...
24567099 - Methods for the study of caspase activation in the xenopus laevis oocyte and egg extract.
24781109 - Toxoplasma effector maf1 mediates recruitment of host mitochondria and impacts the host...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-7
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  -     ISSN:  1096-1186     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Department of Pharmacology, Shanghai JiaoTong, University School of Medicine, Shanghai, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The 17-?-oestradiol inhibits osteoclast activity by increasing the cannabinoid CB2 receptor expressi...
Next Document:  Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hyperte...