Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis
Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis
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DOI：
10.1254/jphs.08332fp
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Kuraishi, Yasushi
中科院分区：
文献类型：
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作者：
Tsujii, Kenichiro;Andoh, Tsugunobu;Kuraishi, Yasushi
这项研究调查了类胰蛋白酶和蛋白酶激活受体(PAR)亚型在NC小鼠自发抓挠中的作用，这是一种瘙痒相关行为。这种品系的小鼠在常规环境中长期饲养时，表现出慢性特应性皮炎和严重的自发抓挠。胰酶样丝氨酸蛋白酶抑制剂甲磺酸那法莫司他(1-10 mg/kg)可剂量依赖性地抑制皮炎小鼠的自发抓挠。皮损中类胰蛋白酶活性增加，在抑制自发划痕的剂量下，奈法莫司他可抑制类胰蛋白酶的活性。酶组织化学显示皮损真皮中甲苯胺蓝染色的细胞明显增多，可能是肥大细胞，具有类胰蛋白酶活性。静脉注射抗PAR(2)抗体可抑制皮炎小鼠的自发抓挠。皮内注射PAR(2)-激活肽SLI-GRL-NH2，但不注射PAR(1)、(3)、(4)-激活肽，在10-100nmol/部位可引起正常小鼠的抓挠。在健康和皮炎小鼠的表皮角质形成细胞中观察到PAR(2)免疫反应。这些结果表明，PAR(2)和丝氨酸蛋白酶(S)，主要是类胰蛋白酶，参与了慢性皮炎的瘙痒。
This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1-10 mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR(2) antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR(2)-activating peptide SLI-GRL-NH2 but not PAR(1), (3), (4)-activating peptides, elicited scratching at doses of 10 - 100 nmol/site in healthy mice. PAR(2)-immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR(2) and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.