The Essential Role of Ca2+ Signals in UVB–Induced IL-1β Secretion in Keratinocytes
| Autor: | Kwang-Hyun Park, Kyu Yun Jang, Dae-Ryoung Park, Ye-Won Kim, Uh-Hyun Kim, Tae-Sik Nam, Hun Taeg Chung |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Reactive oxygen species NADPH oxidase Nicotinic acid adenine dinucleotide phosphate integumentary system biology Cell Biology Dermatology Pannexin Biochemistry Cyclic ADP-ribose Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry 030220 oncology & carcinogenesis biology.protein Secretion Inositol Molecular Biology Intracellular |
| Zdroj: | Journal of Investigative Dermatology. 139:1362-1372 |
| ISSN: | 0022-202X |
| DOI: | 10.1016/j.jid.2018.12.005 |
| Popis: | UVB-induced skin damage is attributable to reactive oxygen species, which are triggered by intracellular Ca2+ signals. However, exactly how the reactive oxygen species are triggered by intracellular Ca2+ upon UVB irradiation remains obscure. Here, we show that UVB induces Ca2+ signals via sequential generation of the following Ca2+ 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 Ca2+ signals and IL-1β secretion in keratinocytes. Furthermore, ablation of CD38 and NADPH oxidase 4 protected against UVB-induced inflammation and IL-1β secretion in the murine epidermis. These results show that UVB induces IL-1β secretion through cross-talk between Ca2+ and reactive oxygen species, providing insight towards potential targets against UVB-induced inflammation. |
| Databáze: | OpenAIRE |
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