ReferenceID 3790
TNF-α-induced CXCL8 production by A549 cells: involvement of the non-neuronal cholinergic system
Pharmacol Res
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 alveol
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3790
- Evidence Id
- 20380
- Core Evidence Id
- 20380
- Source Reference Id
- 864
- Herb2 Reference Id
- HBREF001492
- Subject Paper Key
- HBIN039772_23142559
- Pubmed Id
- 23142559
- Doi
- 10.1016/j.phrs.2012.10.016
- Paper Title
- TNF-α-induced CXCL8 production by A549 cells: involvement of the non-neuronal cholinergic system
- Paper Abstract
- 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.
- Journal
- Pharmacol Res
- Publish Year
- 2013
- Experiment Subject
- cells: a549 human alveolar epithelial cell line
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- TNF-α-induced CXCL8 production by A549 cells: involvement of the non-neuronal cholinergic system
- Bilingual Status
- semi_complete