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Recent evidence has indicated that TRPC6 as a member of the TRPC family plays an important role in airway inflammation, but its precise function in bronchial epithelial cells remains unclear. The aim of this study was to investigate the role of TRPC6 in Toll-like receptor 4 (TLR4)-mediated inflammation in human bronchial epithelial cells stimulated by endotoxin [lipopolysaccharide (LPS)]. Hyp9 is a simplified phloroglucinol derivative of hyperforin that highly selectively activates TRPC6 channels. The results show that the activation of TRPC6 by Hyp9 induced the production of interleukin (IL)-8 and IL-6. LPS was also able to induce the release of IL-8 and IL-6, which was significantly aggravated by Hyp9 and reduced by knockdown of TRPC6. Treatment with LPS not only chronically induced the expression of TRPC6 mRNA and protein in a TLR4-dependent manner but also acutely increased Ca<jats:sup>2+<\/jats:sup> influx through TRPC6 channels. In addition, LPS-induced overexpression of TRPC6 and Ca<jats:sup>2+<\/jats:sup> influx were associated with the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt. Importantly, TRPC6 was required for the activation of ERK1\/2, p38, and NF-\u03baB. In conclusion, these data reveal that LPS induced the overexpression of TRPC6 and TRPC6-dependent Ca<jats:sup>2+<\/jats:sup> influx via the TLR4\/PI3K\/Akt pathway resulting in Ca<jats:sup>2+<\/jats:sup> mobilization, which subsequently promoted the activation of ERK1\/2, p38, and NF-\u03baB and the inflammatory response in bronchial epithelial cells. <\/jats:p>","DOI":"10.1152\/ajpcell.00117.2017","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T23:00:20Z","timestamp":1510786820000},"page":"C278-C288","source":"Crossref","is-referenced-by-count":35,"title":["TRPC6 contributes to LPS-induced inflammation through ERK1\/2 and p38 pathways in bronchial epithelial cells"],"prefix":"10.1152","volume":"314","author":[{"given":"Li-Fen","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences; Affiliated Cancer Hospital and Institute, Guangzhou Medical University, 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