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
复制标题
局部应用内皮素受体拮抗剂可减轻咪喹莫特诱导的银屑病皮肤炎症
DOI：
10.1038/s41598-020-66490-z
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Furue M.
中科院分区：
文献类型：
--
作者：
Nakahara T;Kido-Nakahara M;Ulzii D;Miake S;Fujishima K;Sakai S;Chiba T;Tsuji G;Furue M.
内皮素-1（ET-1）是已知的最强的血管收缩剂，并可引起组胺非依赖性瘙痒。近年来，它在皮肤炎症中的作用开始引起人们的关注。已报道了人银屑病患者表皮中ET-1表达的上调。ET-1可刺激树突状细胞诱导Th 17/1免疫应答。然而，ET-1和ET-1受体之间的相互作用在银屑病发病机制中的作用仍然是难以捉摸的。本研究观察了内皮素1受体拮抗剂对咪喹莫特（IMQ）诱导的小鼠银屑病样皮炎的影响。银屑病相关的细胞因子如IL-17 A和TNF-α诱导人角质形成细胞中ET-1的表达。局部应用选择性内皮素A受体（ETAR）拮抗剂安立生坦可显著减轻MQ诱导的银屑病样皮炎的发展，并显著抑制小鼠模型皮损皮肤中的组织学炎症和细胞因子表达（TNF-α、IL-12 p40、IL-12 p19和IL-17）。此外，局部应用安立生坦抑制淋巴结中树突状细胞的表型和功能活化。我们的研究结果表明，ET-1和ETAR轴在银屑病的发病机制中起着重要作用，是治疗银屑病的潜在治疗靶点。
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.
登录
查看更多内容
影响因子：
20.3
作者：
Nakahara, Takeshi;Uchi, Hiroshi;Houghton, Alan N.
通讯作者：
Houghton, Alan N.
新型 isonahocol E3 在内皮素 1 刺激的人角质形成细胞中表现出抗炎和抗血管生成作用。
影响因子：
5
作者：
S. Sah;Byung;G. Park;Sunghwan Kim;Kyoung Hwa Jang;Ju Eun Jeon;Jongheon Shin;Tae
通讯作者：
Tae
影响因子：
--
作者：
ELTON, TS;OPARIL, S;CHEN, YF
通讯作者：
CHEN, YF
内皮素-1 释放组胺的机制与小鼠骨髓源性肥大细胞中抗原释放的组胺机制不同。
影响因子：
5
作者：
H. Yamamura;T. Nabe;S. Kohno;K. Ohata
通讯作者：
K. Ohata
影响因子：
2.5
作者：
MCCARRON, RM;WANG, L;SPATZ, M
通讯作者：
SPATZ, M