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    
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.
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 :
25107369 - Secreted fibroblast mir-34a induces tubular cell apoptosis in fibrotic kidney.
23395839 - Identification of a molecular profile associated with immune status in first onset schi...
24307759 - Oncostatin m and tlr-4 ligand synergize to induce mcp-1, il-6, and vegf in human aortic...
23181059 - Targeting cytosolic proliferating cell nuclear antigen in neutrophil-dominated inflamma...
23826779 - Immunology of normal and abnormal menstruation.
23533059 - Different molecular weight hyaluronic acid effects on human macrophage interleukin 1β ...
6979589 - Immunologic aspects of otitis media with effusion: characteristics of lymphocyte and ma...
20043099 - The cell toxicity effect of secalonic acid d on gh3 cells and the related mechanisms.
23800719 - The cell-mediated immunity of drosophila melanogaster; hemocyte lineages, immune compar...
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.
Department of Pharmacology, Shanghai JiaoTong, University School of Medicine, Shanghai, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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...