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

To investigate the mechanisms underlying itching in atopic dermatitis, we examined whether thromboxane (TX) A₂, an arachidonic acid metabolite, is involved in spontaneous scratching, an itch-related response, in NC mice with atopic dermatitis-like skin lesions. The TXA₂ 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 TXA₂, were increased in lesional skin. Scratching caused by the PAR2 agonist SLIGRL-NH₂ was suppressed by ONO-3708. SLIGRLNH₂-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 TXA₂, 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 TXA₂, which may be produced via PAR2 activation, is involved in itching in atopic dermatitis. [ABSTRACT FROM AUTHOR]