Department of Dermatology, Hyogo College of Medicine, Hyogo, Japan.
J Dermatol. 2012 Jul;39(7):625-31. doi: 10.1111/j.1346-8138.2011.01462.x. Epub 2011 Dec 29.
Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor which mediates a variety of functions in the skin including cutaneous inflammation. SLIGKV-NH(2) , an agonist peptide for PAR2, enhanced the interleukin (IL)-17-induced production of two CXC chemokines, CXCL1 (GRO-α) and CXCL8 (IL-8), in normal human epidermal keratinocytes (NHEK) in a concentration-dependent manner. The enhanced production of those chemokines was suppressed by a PAR2-specific siRNA. The SLIGKV-NH(2) -induced production of both CXCL1 and CXCL8 was markedly reduced by cyclosporine A. The enhanced production of CXCL1 was suppressed by 1α, 24R-dihydroxyvitamin D(3) , an active form of vitamin D(3) , and weakly by glucocorticoids, dexamethasone and clobetasol propionate, whereas production of CXCL8 was not altered by any of those receptor agonists. In psoriatic skin, the thickened upper spinous layer of the epidermis was positive for PAR2 protein and the expression of the IL17A mRNA was increased. These results suggest that the IL-17-induced pro-inflammatory reaction is enhanced by the activation of PAR2 in keratinocytes, and that the effect of PAR2 is differentially modulated by cyclosporine A, the active form of vitamin D(3) and glucocorticoids.
蛋白酶激活受体 2（PAR2）是一种 G 蛋白偶联受体，在皮肤中具有多种功能，包括皮肤炎症。PAR2 的激动肽 SLIGKV-NH₂，以浓度依赖的方式增强了正常人类表皮角质形成细胞（NHEK）中白细胞介素（IL）-17 诱导的两种 CXC 趋化因子 CXCL1（GRO-α）和 CXCL8（IL-8）的产生。PAR2 特异性 siRNA 抑制了这些趋化因子的产生。SLIGKV-NH₂诱导的 CXCL1 和 CXCL8 的产生均明显被环孢素 A 抑制。CXCL1 的产生被维生素 D3 的活性形式 1α,24R-二羟维生素 D3 抑制，糖皮质激素地塞米松和丙酸氯倍他索抑制作用较弱，而 CXCL8 的产生不受这些受体激动剂的影响。在银屑病皮肤中，表皮的增厚棘状上层层阳性表达 PAR2 蛋白，IL17A mRNA 的表达增加。这些结果表明，角质形成细胞中 PAR2 的激活增强了 IL-17 诱导的促炎反应，而 PAR2 的作用可被环孢素 A、维生素 D3 的活性形式和糖皮质激素差异调节。
