TRPV4 channel-regulated ATP release contributes to γ-irradiation-induced production of IL-6 and IL-8 in epidermal keratinocytes.

TRPV4 channel-regulated ATP release contributes to γ-irradiation-induced production of IL-6 and IL-8 in epidermal keratinocytes. Biol Pharm Bull. 2018 Jul 19;: Authors: Ohsaki A, Tanuma SI, Tsukimoto M Abstract External stimuli, such as radiation, induce inflammatory cytokine and chemokine production in skin, but the mechanisms involved are not completely understood. We previously showed that the P2Y11 nucleotide receptor, p38 MAPK and NF-κB all participate in IL-6 production induced by γ-irradiation. Here, we focused on the transient receptor potential V4 (TRPV4) channel, which is expressed in skin keratinocytes and has been reported to play a role in inflammation. We found that irradiation of human epidermal keratinocytes HaCaT cells with 5 Gy of γ-rays (137Cs: 0.75 Gy/min) induced IL-6 and IL-8 production. HaCaT cells treated with TRPV4 channel agonist GSK1016790A also showed increased IL-6 and IL-8 production. In both cases, IL-6/IL-8 production was not increased at 24 h after stimulation, but was increased at 48 h. ATP was released from cells exposed to γ-irradiation or TRPV4 channel agonist, and the release was suppressed by TRPV4 channel inhibitors. The γ-irradiation-induced increase in IL-6 and IL-8 production was suppressed by apyrase (ecto-nucleotidase), NF157 (selective P2Y11 receptor antagonist) and SB203580 (p38 MAPK inhibitor). GSK1016790A-induced IκB decomposition, which causes NF-κB activation was suppressed b...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research