Phospholipase Cε has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC

Abstract

Phospholipase C (PLC) is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. We previously demonstrated that PLC has an important role in the development of phorbol ester-induced skin inflammation. In this study, we investigated the role of PLC in ultraviolet (UV) B-induced acute inflammatory reactions in the skin. Wild-type (PLCε+/+) and PLCε gene knockout (PLCε-/-) 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 PLCε+/+ 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 PLCε-/- mice, UVB (1 or 2.5 kJ/m 2)-induced neutrophil infiltration was markedly suppressed compared with PLCε+/+ mice. The suppression of neutrophil infiltration in PLCε-/- 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 PLCε-dependent manner after UVB irradiation, and the UVB-induced upregulation of CXCL1/KC in these cells was significantly abolished by a PLCε inhibitor. Furthermore, UVB-induced epidermal thickening was noticeably reduced in the skin of PLCε -/- mice. These results indicate that PLCε 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. © 2011 USCAP, Inc All rights reserved.