title: Phospholipase Cɛ has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC.
abstract: Phospholipase C (PLC) ɛ is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. We previously demonstrated that PLCɛ has an important role in the development of phorbol ester-induced skin inflammation. In this study, we investigated the role of PLCɛ in ultraviolet (UV) B-induced acute inflammatory reactions in the skin. Wild-type (PLCɛ+/+) and PLCɛ gene knockout (PLCɛ⁻/⁻) mice were irradiated with a single dose of UVB at 1, 2.5, and 10 kJ/m² on the dorsal area of the skin, and inflammatory reactions in the skin were histologically evaluated up to 168 h after irradiation. In PLCɛ+/+ mice, irradiation with 1 and 2.5 kJ/m² UVB resulted in dose-dependent neutrophil infiltration in the epidermis at 24 and 48 h after irradiation. When mice were irradiated with 10 kJ/m² of UVB, most mice developed skin ulcers by 48 h and these ulcers became more severe at 168 h. In PLCɛ⁻/⁻ mice, UVB (1 or 2.5 kJ/m²)-induced neutrophil infiltration was markedly suppressed compared with PLCɛ+/+ mice. The suppression of neutrophil infiltration in PLCɛ⁻/⁻ 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 PLCɛ-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 PLCɛ⁻/⁻ mice. These results indicate that PLCɛ 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.
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan. oka@med.kobe-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
authors.forename: Hironori
authors.initials: H
authors.lastname: Edamatsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Kunisada
authors.forename: Lizhi
authors.initials: L
authors.lastname: Hu
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takenaka
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Tohru
authors.initials: T
authors.lastname: Kataoka
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics*; D017931:DNA Primers; D003872:Dermatitis / Q000209:etiology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology*; D054801:Phosphoinositide Phospholipase C / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D017931:DNA Primers; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon