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

Abstract

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. 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 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.

• Authors: Tsugunobu Andoh, Ai Yamamoto, Satomi Haza, Koh-Ichi Yuhki, Fumitaka Ushikubi, Shu Narumiya, Yasushi Kuraishi
• Journal: Acta dermato-venereologica (Acta Derm Venereol) Vol. 96 Issue 7 Pg. 899-904 (Nov 02 2016) ISSN: 1651-2057 [Electronic] Sweden
• PMID: 27066774 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Methacrylates
• Oligopeptides
• RNA, Messenger
• Receptor, PAR-2
• seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
• Thromboxane A2
• ONO 3708
• ozagrel

Topics

• Animals
• Dermatitis, Atopic (drug therapy, metabolism)
• Keratinocytes (metabolism)
• Male
• Methacrylates (pharmacology)
• Mice
• Oligopeptides (adverse effects, pharmacology)
• Pruritus (drug therapy, metabolism)
• RNA, Messenger (metabolism)
• Receptor, PAR-2 (antagonists & inhibitors)
• Thromboxane A2 (analogs & derivatives, metabolism, pharmacology)