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隐丹参酮通过抑制肥大细胞中的脾酪氨酸激酶和酪氨酸蛋白激酶磷酸化来抑制 IgE 介导的脱颗粒。

Cryptotanshinone inhibits IgE‑mediated degranulation through inhibition of spleen tyrosine kinase and tyrosine‑protein kinase phosphorylation in mast cells.

机构信息

Department of Biological Science, Sookmyung Women's University, Seoul 04310, Republic of Korea.

出版信息

Mol Med Rep. 2018 Jul;18(1):1095-1103. doi: 10.3892/mmr.2018.9042. Epub 2018 May 22.

Abstract

Atopic dermatitis (AD) is a type of chronic skin inflammation and one of the most common relapsing allergic diseases, which presents with a severe rash and itchy skin lesions. The pathogenesis of AD is primarily associated with hyper‑activated mast cells, which makes them an effective treatment target. After cross‑linking the antigen/immunoglobulin (Ig) E complex binds to its high affinity receptor FcεRl on the surface of mast cells. The cells subsequently secrete excessive pro‑inflammatory mediators, including histamine and cytokines, which lead to pruritus and immune cell infiltration in the skin lesions. The present study screened natural compounds that have an inhibitory effect on IgE/antigen‑mediated secretory activity. It was revealed that cryptotanshinone (CRT), a natural compound extracted from Salvia miltiorrhiza Bunge, had inhibitory effects on the IgE/antigen complex. The underlying mechanism by which CRT exerted an anti‑allergy/inflammatory function was investigated using rat basophilic leukaemia (RBL) cells for degranulation assays and a 1‑chloro‑2,4‑dinitrobenzene (DNCB)‑induced AD Balb/c mouse model for in vivo study. CRT effectively mitigated the secretion of pro‑inflammatory cytokines, including tumor necrosis factor‑α and interleukin 1β, as well as immune cell infiltration into skin lesions in a mouse model of AD‑like skin disease induced by dinitrochlorobenzene. The inhibitory effect of CRT on IgE‑mediated mast cell degranulation was mediated by the inhibition of tyrosine kinase‑dependent degranulation signalling pathways involving spleen tyrosine kinase and Lyn. The present study revealed CRT as an inhibitor of mast cell degranulation. Therefore, CRT may be considered for development as a therapeutic drug to treat IgE‑mediated skin diseases.

摘要

特应性皮炎(AD)是一种慢性皮肤炎症,也是最常见的复发性过敏性疾病之一,表现为严重的皮疹和瘙痒性皮损。AD 的发病机制主要与高活性肥大细胞有关,使其成为有效的治疗靶点。抗原/免疫球蛋白(Ig)E 复合物交联后,与肥大细胞表面的高亲和力受体 FcεRl 结合。细胞随后分泌过多的促炎介质,包括组胺和细胞因子,导致瘙痒和免疫细胞浸润皮损。本研究筛选了对 IgE/抗原介导的分泌活性具有抑制作用的天然化合物。结果表明,隐丹参酮(CRT),一种从丹参中提取的天然化合物,对 IgE/抗原复合物具有抑制作用。使用大鼠嗜碱性白血病(RBL)细胞进行脱颗粒测定和 1-氯-2,4-二硝基苯(DNCB)诱导的 AD Balb/c 小鼠模型进行体内研究,探讨了 CRT 发挥抗过敏/抗炎功能的潜在机制。CRT 有效减轻了促炎细胞因子(包括肿瘤坏死因子-α和白细胞介素-1β)的分泌以及免疫细胞向 AD 样皮肤病诱导的 DNCB 小鼠模型皮损中的浸润。CRT 对 IgE 介导的肥大细胞脱颗粒的抑制作用是通过抑制脾酪氨酸激酶和 Lyn 参与的酪氨酸激酶依赖性脱颗粒信号通路介导的。本研究揭示了 CRT 是肥大细胞脱颗粒的抑制剂。因此,CRT 可被视为治疗 IgE 介导的皮肤疾病的治疗药物。

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