Thromboxane A2 is Involved in Itch-associated Responses in Mice with Atopic Dermatitis-like Skin Lesions

被引:10
作者
Andoh, Tsugunobu [1 ]
Yamamoto, Ai [1 ]
Haza, Satomi [1 ]
Yuhki, Koh-ichi [2 ]
Ushikubi, Fumitaka [2 ]
Narumiya, Shu [3 ]
Kuraishi, Yasushi [4 ]
机构
[1] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Appl Pharmacol, 2630 Sugitani, Toyama 9301094, Japan
[2] Asahikawa Med Univ, Dept Pharmacol, Asahikawa, Hokkaido, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto, Japan
[4] Tokyo Med & Dent Univ, Res Adm Div, Tokyo, Japan
关键词
itch; thromboxane A(2); TP receptor; thromboxane synthase; atopic dermatitis; proteinase-activated receptor 2; PROTEINASE-ACTIVATED RECEPTOR-2; SCRATCHING BEHAVIOR; CONDUCTION-VELOCITY; DOUBLE-BLIND; NC MICE; EXPRESSION; ANTAGONIST; CELLS;
D O I
10.2340/00015555-2437
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
To investigate the mechanisms underlying itching in atopic dermatitis, we examined whether thromboxane (TX) A(2), an arachidonic acid metabolite, is involved in spontaneous scratching, an itch-related response, in NC mice with atopic dermatitis-like skin lesions. The TXA(2) receptor (TP) antagonist ONO-3708 inhibited the spontaneous scratching. The mRNA expression of TX synthase (TXSyn) distributed mainly in epidermis and the concentration of TXB2, a metabolite of TXA(2), were increased in lesional skin. Scratching caused by the PAR2 agonist SLIGRL-NH2 was suppressed by ONO-3708. SLIGRL-NH2-induced scratching decreased approximately 75% in TP-deficient mice, compared to wild-type mice. In primary cultures of mouse keratinocytes, SLIGRL-NH2 induced the production of TXA(2), as evidenced by the increased TXB2, which was inhibited by the TXSyn inhibitor sodium ozagrel and a PAR2-neutralizing antibody. Taken together, these results suggest that epidermal TXA(2), which may be produced via PAR2 activation, is involved in itching in atopic dermatitis.
引用
收藏
页码:899 / 904
页数:6
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