Regulation of Particulate Matter-Induced Mucin Secretion by Transient Receptor Potential Vanilloid 1 Receptors
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Regulation of Particulate Matter-Induced Mucin Secretion by Transient Receptor Potential Vanilloid 1 Receptors Hongmei Yu,1 Qi Li,1 Victor P. Kolosov,2 Juliy M. Perelman,2 and Xiangdong Zhou1,3,4
Abstract—Exposure to airborne particulate matter (PM) is a worldwide health problem. Previous studies have reported that PMs induced depolarizing currents and increased intracellular Ca2+ in human bronchial epithelial cells. Ca2+ 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. Ca2+ 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 Ca2+ influx and cAMP increase through TRPV1 receptors. Mucin secretion was completely inhibited by TRPV1 receptor antagonist capsazepine. Removal of Ca2+ by Ca2+ chelator BAPTA or inhibition of protein kinase A (PKA) by the PKA inhibitors H-89 each partially reduced PC2s-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 Ca2+ influx and cAMP/PKA pathway by TRPV1 receptors in human bronchial epithelial cells, thereby providing a potential mechanism to reduce PM toxicity. KEY WORDS: particulate matter; TRPV1; calcium; cyclic adenosine monophosphate; mucus.
INTRODUCTION Inhalation of approximately 12,000 L of air a day bombards the airway epithelium with up to 25 million particles an hour [1]. The first-line defense against inhaled insult impinging on and damaging the airway epithelium is the production of mucus. Airway mucus is an integral component of the mucociliary clearance system in the trachea and bronchi and thus serves to protect the lower airways and alveoli from impingement of particulate matter (PM) and pathogens. However, mucin secretion is abnormally augmented in diseases, 1
Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China 2 Far Eastern Scientific Center of Physiology and Pathology of Respiration, Siberian Branch, Russian Academy of Medical Sciences, Blagoveshchensk( Russia 3 No.74, Linjiang Road, Yuzhong District( Chongqing 400010, China 4 To whom correspondence should be addressed at No.74, Linjiang Road, Yuzhong District( Chongqing 400010, China. E-mail: [email protected]
such as asthma [2], chronic obstructive pulmonary disease [3, 4], and cystic fibrosis [5], increasing morbidity and mortality in these patients [6]. Excess mucus can contribute to obstruction, susceptibility to infection, and even to destruction of airway walls and contiguous tissues. The major component
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