title: Regulation of particulate matter-induced mucin secretion by transient receptor potential vanilloid 1 receptors.
abstract: Exposure to airborne particulate matter (PM) is a worldwide health problem. Previous studies have reported that PMs induced depolarizing currents and increased intracellular Ca(2+) in human bronchial epithelial cells. Ca(2+) plays important role in the regulation of mucus exocytosis, and mucin hypersecretion is a key pathological feature of inflammatory respiratory diseases. To explore more mechanisms underlying PM toxicity, we measured PM-induced mucin secretion in human bronchial epithelial (16HBE) cells. MUC5AC secretion and cyclic adenosine monophosphate (cAMP) level were detected by ELISA. Transient receptor potential vanilloid (TRPV)1 inward currents were examined by electrophysiology. Ca(2+) concentration was assessed by laser scanning confocal microscope. Exposure of PMs to 16HBE cells was found to induce mucin secretion, as a consequence of sustained Ca(2+) influx and cAMP increase through TRPV1 receptors. Mucin secretion was completely inhibited by TRPV1 receptor antagonist capsazepine. Removal of Ca(2+) by Ca(2+) chelator BAPTA or inhibition of protein kinase A (PKA) by the PKA inhibitors H-89 each partially reduced PC(2)s-induced mucin secretion. The combination of BAPTA and H-89 completely prevented mucin secretion mediated by PMs. These results suggest that PM induces mucin secretion through Ca(2+) influx and cAMP/PKA pathway by TRPV1 receptors in human bronchial epithelial cells, thereby providing a potential mechanism to reduce PM toxicity.
authors: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors: Hongmei
authors: H
authors: Yu
authors: Qi
authors: Q
authors: Li
authors: Victor P
authors: VP
authors: Kolosov
authors: Juliy M
authors: JM
authors: Perelman
authors: Xiangdong
authors: X
authors: Zhou
mesh_terms: D000393:Air Pollutants; D001980:Bronchi / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002461:Cell Line, Transformed; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004781:Environmental Exposure; D004847:Epithelial Cells; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D018613:Microscopy, Confocal; D055271:Mucin 5AC / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D052638:Particulate Matter; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D002614:Chelating Agents; D007546:Isoquinolines; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D052638:Particulate Matter; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D004533:Egtazic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C071423:capsazepine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002211:Capsaicin; D002118:Calcium