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Regulation of Particulate Matter-Induced Mucin Secretion by Transient Receptor Potential Vanilloid 1 Receptors

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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.

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Acknowledgments

This work was supported by grant from the National Nature Science Foundation of China (no. 31171346), and China–Russia Cooperation Research Foundation (NSFC 31211120168).

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Correspondence to Xiangdong Zhou.

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Yu, H., Li, Q., Kolosov, V.P. et al. Regulation of Particulate Matter-Induced Mucin Secretion by Transient Receptor Potential Vanilloid 1 Receptors. Inflammation 35, 1851–1859 (2012). https://doi.org/10.1007/s10753-012-9506-x

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