Abstract
We investigated the role of tumor necrosis factor-α (TNFα) in activating the store-operated Ca2+ channels in CCD-18Co cells via the expression of canonical transient receptor potential (TRPC) channel isoforms. CCD-18Co cells were derived from human colon and exhibit many properties typical of intestinal subepithelial myofibroblasts, which play crucial roles in intestinal homeostasis, inflamation, and neoplasia. 24hr treatment with TNFα activated store dependent Ca2+ influx with increased expression of TRPC1 in CCD-18Co. Simultaneously, cyclooxygenase (COX)-dependent PGE2 production was significantly enhanced. Part of the production has been shown to be dependent on Ca2+. TNFα-induced PGE2 production was significantly augmented by siRNA knockdown of TRPC1.From these results, we suggest that myofibroblasts could be the important target of inflammatory cytokines in the colon. The sustained elevation of [Ca2+]i in CCD-18Co may serve as the essential mechanism to regulate PGE2 production in response to cytokines. [J Physiol Sci. 2008;58 Suppl:S51]
