Cathepsin E induces itch-related response through the production of endothelin-1 in mice

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• 作者：Tsugunobu Andoh^a ; Tetsuro Yoshida^a ; Jung-Bum Lee^b ; Yasushi Kuraishi^a ; ^{kuraisiy@pha.u-toyama.ac.jp}
• 关键词：Cathepsin E ; Endothelin-1 ; Itch ; Keratinocyte ; Mast cell ; Scratching
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：5 July, 2012
• 卷：686
• 期：1-3
• 页码：16-21
• 文件大小：401 K

摘要

This study investigated the pruritogenic potency of cathepsin E, an aspartic protease, and its mechanisms in mice. An intradermal injection of cathepsin E to the rostral back elicited scratching, an itch-associated response, of the injection site. This action was inhibited by the aspartic protease inhibitor pepstatin A, the endothelin ET_A receptor antagonist BQ-123, and the opioid receptor antagonists naltrexone and naloxone, but not by the H₁ histamine receptor antagonist terfenadine, the proteinase-activated receptor-2 antagonist FSLLRY-NH₂, or mast cell deficiency. Pepstatin A inhibited scratching induced by intradermal injection of the mast-cell degranulator compound 48/80, but not by tryptase, a mast-cell mediator. An intradermal injection of cathepsin E increased endothelin-1 levels in the skin at the injection site. Preproendothelin-1 mRNA was present in primary cultures of keratinocytes, and immunohistochemistry using an antibody recognizing endothelin-1 and big-endothelin-1 revealed immunoreactivity in the epidermis, especially in the prickle and granular cell layers, but not in the basal cell layer. These results suggest that cathepsin E is an endogenous itch inducer, and that its action is mediated at least in part by the production of endothelin-1 in the epidermis.