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  • Topical application of endothelin receptor a antagonist attenuates imiquimod-induced psoriasiform skin inflammation.

Topical application of endothelin receptor a antagonist attenuates imiquimod-induced psoriasiform skin inflammation.

Scientific reports (2020-06-13)
Takeshi Nakahara, Makiko Kido-Nakahara, Dugarmaa Ulzii, Sho Miake, Kei Fujishima, Sawako Sakai, Takahito Chiba, Gaku Tsuji, Masutaka Furue
ABSTRACT

Endothelin-1 (ET-1) is well known as the most potent vasoconstrictor, and can evoke histamine-independent pruritus. Recently, its involvement in cutaneous inflammation has begun to draw attention. The upregulation of ET-1 expression in the epidermis of human psoriasis patients has been reported. It was also demonstrated that ET-1 can stimulate dendritic cells to induce Th17/1 immune responses. However, the role of the interaction between ET-1 and ET-1 receptors in the pathogenesis of psoriasis remains elusive. Here, we investigated the effects of ET-1 receptor antagonist on imiquimod (IMQ) -induced psoriasiform dermatitis in mouse. Psoriasis-related cytokines such as IL-17A and TNF-α induced ET-1 expression in human keratinocytes. Topical application of selective endothelin A receptor (ETAR) antagonist ambrisentan significantly attenuated the development of IMQ-induced psoriasiform dermatitis and also significantly inhibited the histological inflammation and cytokine expression (TNF-α, IL-12p40, IL-12 p19, and IL-17) in the lesional skin of the mouse model. Furthermore, topical application of ambrisentan suppressed phenotypic and functional activation of dendritic cells in lymph nodes. Our findings indicate that the ET-1 and ETAR axis plays an important role in the pathogenesis of psoriasis and is a potential therapeutic target for treating psoriasis.

MATERIALS
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Brand
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Sigma-Aldrich
BQ-788, ≥95%, solid