Phospholipase Cε has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC
Phospholipase Cε has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC
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DOI：
10.1038/labinvest.2011.10
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发表时间：
2011-05-01
影响因子：
5
通讯作者：
Nishigori, Chikako
中科院分区：
文献类型：
--
作者：
Oka, Masahiro;Edamatsu, Hironori;Nishigori, Chikako
磷脂酶C（PLC）是由Ras和Rap等小GTP酶调控的磷酸肌醇特异性PLC。我们先前证明PLC在佛波酯诱导的皮肤炎症的发展中具有重要作用。在这项研究中，我们研究了PLC的作用，在紫外线（UV）B诱导的皮肤急性炎症反应。野生型（PLC β（+/+））和PLC β基因敲除（PLC β（-/-））小鼠用1、2.5和10 kJ/m2的UVB单剂量照射背部皮肤，并在照射后168 h内对皮肤的炎症反应进行组织学评价。用1和2.5 kJ/m2 UVB照射PLC +/+小鼠，在照射后24和48 h，表皮中出现剂量依赖性中性粒细胞浸润。当用10 kJ/m2的UVB照射小鼠时，大多数小鼠在48 h内出现皮肤溃疡，这些溃疡在168 h时变得更加严重。在PLC阳性（-/-）小鼠中，UVB（1或2.5 kJ/m2）诱导的中性粒细胞浸润与PLC阴性（+/+）小鼠相比明显受到抑制。在PLC β（-/-）小鼠中中性粒细胞浸润的抑制伴随着UVB诱导的CXCL 1/角质形成细胞衍生的趋化因子（KC）（一种有效的中性粒细胞趋化因子）在整个皮肤中的产生的衰减。UVB照射后，培养的表皮角质形成细胞和真皮成纤维细胞以PLC ε依赖性方式产生CXCL 1/KC，并且UVB诱导的这些细胞中CXCL 1/KC的上调被PLC抑制剂显着消除。此外，UVB诱导的表皮增厚明显减少在皮肤中的PLC pcs（-/-）小鼠。这些结果表明，PLC β 1在UVB诱导的急性炎症反应，如中性粒细胞浸润和表皮增厚，至少部分调节皮肤细胞，如角质形成细胞和成纤维细胞中的CXCL 1/KC的表达具有至关重要的作用。实验室调查（2011）91，711-718; doi：10.1038/labinvest.2011.10; 2011年2月14日在线发表
Phospholipase C (PLC) epsilon is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. We previously demonstrated that PLC epsilon has an important role in the development of phorbol ester-induced skin inflammation. In this study, we investigated the role of PLC epsilon in ultraviolet (UV) B-induced acute inflammatory reactions in the skin. Wild-type (PLC epsilon(+/+)) and PLC epsilon gene knockout (PLC epsilon(-/-)) 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 PLC epsilon(+/+) 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 PLC epsilon(-/-) mice, UVB (1 or 2.5 kJ/m(2))-induced neutrophil infiltration was markedly suppressed compared with PLC epsilon(+/+) mice. The suppression of neutrophil infiltration in PLC epsilon(-/-) 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 PLC epsilon-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 PLC epsilon(-/-) mice. These results indicate that PLC epsilon 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. Laboratory Investigation (2011) 91, 711-718; doi:10.1038/labinvest.2011.10; published online 14 February 2011