Topical application of endothelin receptor A antagonist attenuates imiquimod-induced psoriasiform skin inflammation
Autor: | Gaku Tsuji, Masutaka Furue, Kei Fujishima, Makiko Kido-Nakahara, Takahito Chiba, Sawako Sakai, Dugarmaa Ulzii, Sho Miake, Takeshi Nakahara |
---|---|
Rok vydání: | 2020 |
Předmět: |
Endothelin Receptor Antagonists
0301 basic medicine Ambrisentan medicine.drug_class Administration Topical lcsh:Medicine Inflammation Imiquimod Article Mice 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Psoriasis Animals Humans Medicine lcsh:Science Receptor Psoriasiform Dermatitis Skin Multidisciplinary Endothelin-1 Phenylpropionates Receptors Endothelin business.industry lcsh:R medicine.disease Receptor antagonist Skin diseases Pyridazines 030104 developmental biology Gene Expression Regulation Cancer research Cytokines lcsh:Q medicine.symptom business Endothelin receptor medicine.drug |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |