| First Author | Oka M | Year | 2011 |
| Journal | Lab Invest | Volume | 91 |
| Issue | 5 | Pages | 711-8 |
| PubMed ID | 21321537 | Mgi Jnum | J:171257 |
| Mgi Id | MGI:4949046 | Doi | 10.1038/labinvest.2011.10 |
| Citation | Oka M, et al. (2011) Phospholipase Cvarepsilon has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC. Lab Invest 91(5):711-8 |
| abstractText | Phospholipase C (PLC) varepsilon is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. We previously demonstrated that PLCvarepsilon has an important role in the development of phorbol ester-induced skin inflammation. In this study, we investigated the role of PLCvarepsilon in ultraviolet (UV) B-induced acute inflammatory reactions in the skin. Wild-type (PLCvarepsilon(+/+)) and PLCvarepsilon gene knockout (PLCvarepsilon(-/-)) mice were irradiated with a single dose of UVB at 1, 2.5, and 10 kJ/m(2) on the dorsal area of the skin, and inflammatory reactions in the skin were histologically evaluated up to 168 h after irradiation. In PLCvarepsilon(+/+) mice, irradiation with 1 and 2.5 kJ/m(2) UVB resulted in dose-dependent neutrophil infiltration in the epidermis at 24 and 48 h after irradiation. When mice were irradiated with 10 kJ/m(2) of UVB, most mice developed skin ulcers by 48 h and these ulcers became more severe at 168 h. In PLCvarepsilon(-/-) mice, UVB (1 or 2.5 kJ/m(2))-induced neutrophil infiltration was markedly suppressed compared with PLCvarepsilon(+/+) mice. The suppression of neutrophil infiltration in PLCvarepsilon(-/-) mice was accompanied by attenuation of UVB-induced production of CXCL1/keratinocyte-derived chemokine (KC), a potent chemokine for neutrophils, in the whole skin. Cultured epidermal keratinocytes and dermal fibroblasts produced CXCL1/KC in a PLCvarepsilon-dependent manner after UVB irradiation, and the UVB-induced upregulation of CXCL1/KC in these cells was significantly abolished by a PLC inhibitor. Furthermore, UVB-induced epidermal thickening was noticeably reduced in the skin of PLCvarepsilon(-/-) mice. These results indicate that PLCvarepsilon has a crucial role in UVB-induced acute inflammatory reactions such as neutrophil infiltration and epidermal thickening by at least in part regulating the expression of CXCL1/KC in skin cells such as keratinocytes and fibroblasts. |
