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呋喃他酮通过抑制肥大细胞中的 Lyn/Syk 通路来抑制 IgE 介导的过敏反应。

Furaltadone suppresses IgE-mediated allergic response through the inhibition of Lyn/Syk pathway in mast cells.

机构信息

Department of Immunology, College of Medicine, Konkuk University, Chungju 27478, Republic of Korea.

College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.

出版信息

Eur J Pharmacol. 2018 Jun 5;828:119-125. doi: 10.1016/j.ejphar.2018.03.035. Epub 2018 Mar 26.

Abstract

Mast cells are critical cells that prompt various allergic response-inducing factors, contributing to allergic diseases. While used as an antibiotic for livestock, there is no study on the effect of furaltadone on allergic response. This study investigated the effect of furaltadone on mast cells and passive cutaneous anaphylaxis (PCA). Furaltadone inhibited the degranulation of mast cells stimulated by antigen (IC, ~ 3.9 μM), and also suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-4 in a concentration dependent manner. In addition, furaltadone inhibited allergic responses in an acute allergy animal model, PCA. Further investigation on the mechanism for these inhibitory effects of furaltadone found that the activities of Lyn/Syk and Syk-dependent downstream proteins such as mitogen-activated protein (MAP) kinases were inhibited by furaltadone in mast cells. Taken together, this study demonstrates that furaltadone inhibits the activation of mast cells by antigen via the suppression of the Lyn/Syk pathway and ameliorates allergic responses in vivo.

摘要

肥大细胞是触发各种过敏原的关键细胞,导致过敏疾病。虽然它被用作家畜的抗生素,但关于呋喃它酮对过敏反应的影响尚无研究。本研究探讨了呋喃它酮对肥大细胞和被动皮肤过敏反应(PCA)的影响。呋喃它酮抑制了抗原刺激的肥大细胞脱颗粒(IC,约 3.9µM),并呈浓度依赖性抑制肿瘤坏死因子(TNF)-α和白细胞介素(IL)-4 的产生。此外,呋喃它酮抑制了急性过敏动物模型 PCA 中的过敏反应。进一步研究呋喃它酮这些抑制作用的机制发现,在肥大细胞中,呋喃它酮抑制 Lyn/Syk 活性和 Syk 依赖性下游蛋白(如丝裂原激活蛋白激酶)的活性。综上所述,本研究表明,呋喃它酮通过抑制 Lyn/Syk 途径抑制抗原激活的肥大细胞,改善体内过敏反应。

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