| First Author | Park KH | Year | 2019 |
| Journal | J Invest Dermatol | Volume | 139 |
| Issue | 6 | Pages | 1362-1372 |
| PubMed ID | 30578820 | Mgi Jnum | J:295073 |
| Mgi Id | MGI:6459615 | Doi | 10.1016/j.jid.2018.12.005 |
| Citation | Park KH, et al. (2019) The Essential Role of Ca(2+) Signals in UVB-Induced IL-1beta Secretion in Keratinocytes. J Invest Dermatol 139(6):1362-1372 |
| abstractText | UVB-induced skin damage is attributable to reactive oxygen species, which are triggered by intracellular Ca(2+) signals. However, exactly how the reactive oxygen species are triggered by intracellular Ca(2+) upon UVB irradiation remains obscure. Here, we show that UVB induces Ca(2+) signals via sequential generation of the following Ca(2+) messengers: inositol 1,4,5-trisphosphate, nicotinic acid adenine dinucleotide phosphate, and cyclic ADP-ribose. UVB induced H2O2 production through NADPH oxidase 4 activation, which is downstream to inositol 1,4,5-trisphosphate and nicotinic acid adenine dinucleotide phosphate. H2O2 derived from NADPH oxidase 4 activated CD38 to produce cyclic ADP-ribose. UVB first evoked the pannexin channel to release ATP, which acts on P2X7 receptor to generate inositol 1,4,5-trisphosphate. Inhibitors of these messengers, as well as antioxidants, blocked UVB-induced Ca(2+) signals and IL-1beta secretion in keratinocytes. Furthermore, ablation of CD38 and NADPH oxidase 4 protected against UVB-induced inflammation and IL-1beta secretion in the murine epidermis. These results show that UVB induces IL-1beta secretion through cross-talk between Ca(2+) and reactive oxygen species, providing insight towards potential targets against UVB-induced inflammation. |
