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Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity.
小热休克蛋白 CRYAB 抑制肠黏膜炎症反应,并通过抑制 ikk β 活性保护屏障完整性。

摘要

Alpha B-crystallin (CRYAB) is an important member of the small heat shock protein family, and plays a protective and therapeutic role in neurological inflammation. CRYAB expression was assessed in cultured HT29 and Caco-2 cells and inflamed mucosa of patients with inflammatory bowel disease (IBD) and colitis models in mice. Lentivirus-overexpressing and CRSIPR/Cas9 systems were used in different cells to upregulate and silence CRYAB expression, respectively. Cell permeable recombined fusion protein TAT-CRYAB was injected intraperitoneally into dextran sulfate sodium (DSS)- or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice to assess its anti-inflammatory effects. CRYAB was found to be significantly decreased in the inflamed mucosa from IBD patients and DSS-induced colitis in mice, and negatively correlated with the levels of TNF-α and IL-6, respectively. Enforced expression of CRYAB suppressed expression of proinflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, and IL-8) via inhibiting the IKK complex formation, whereas lack of CRYAB expression markedly enhanced proinflammatory responses. Consistently, administration of TAT-CRYAB fusion protein significantly alleviated DSS- or TNBS-induced colitis in mice and protected intestinal barrier integrity. CRYAB regulates inflammatory response in intestinal mucosa by inhibiting IKKβ-mediated signaling and may serve as a novel therapeutic approach in the treatment of IBD.

译文

α B-晶体蛋白 (CRYAB) 是小热休克蛋白家族的重要成员,在神经系统炎症中发挥保护和治疗作用。在小鼠炎症性肠病 (IBD) 和结肠炎模型患者的培养的 HT29 和 Caco-2 细胞以及发炎粘膜中评估 CRYAB 的表达。慢病毒过表达和 CRSIPR/Cas9 系统分别用于不同细胞的上调和沉默 CRYAB 的表达。将细胞渗透性重组融合蛋白 TAT-CRYAB 腹腔注射到葡聚糖硫酸钠 (DSS)-或 2,4,6-三硝基苯磺酸 (TNBS) 诱导的小鼠结肠炎中,以评估其抗炎作用。在 IBD 患者和 DSS 诱导的小鼠结肠炎的发炎粘膜中发现 CRYAB 显著降低,并且分别与 TNF-α 和 IL-6 的水平呈负相关。CRYAB 的强制表达通过抑制 IKK 复合物的形成来抑制促炎细胞因子的表达 (例如,TNF-α 、 IL-6 、 IL-1 β 和 IL-8), 而缺乏 CRYAB 表达显著增强促炎症反应。一致地,TAT-CRYAB 融合蛋白的管理显著缓解了 DSS 或 TNBS 诱导的小鼠结肠炎,并保护了肠屏障的完整性。CRYAB 通过抑制 ikk β 介导的信号调节肠黏膜的炎症反应,可能成为治疗 IBD 的一种新的治疗方法。

Heat shock protein

内分泌 蛋白 临床研究术语
概述  :  

热休克蛋白(HSP)是细胞响应暴露于压力条件而产生的蛋白质家族。它们首先相关于热休克,但现在已知在包括暴露于冷,UV光和伤口愈合或组织重塑期间也可以产生。该组的许多成员通过稳定新蛋白以确保正确折叠或通过帮助重新折叠受细胞应激破坏的蛋白来执行伴侣功能。这种表达的增加在转录上规范的。热激蛋白的急剧上调是热激反应的关键部分,主要是由热激因子(HSF)引起的。从细菌到人类,几乎所有活生物体中都发现了HSP 。 功能 HSPs不仅在热激

heat   英 /hiːt/   美 /hiːt/

释    义   n. 高温;压力;热度;热烈

               vt. 使激动;把…加热

例    句   Most plastics do not readily conduct heat or electricity.大多数塑料不易传热或导电。

 

shock   英 /ʃɒk/   美 /ʃɑːk/

释    义   n. 休克;震惊;震动;打击;禾束堆

               vt. 使休克;使震惊;使震动;使受电击;把…堆成禾束堆

               vi. 感到震惊;受到震动;堆成禾束堆

               adj. 浓密的;蓬乱的

例    句   The operation was successfully performed, but the patient suffered from shock.手术进行良好, 但病人发生了休克现象。

 

protein   英 /ˈprəʊtiːn/   美 /ˈproʊtiːn/

释    义   n. 蛋白质;朊

               adj. 蛋白质的

例    句   If you like these, they can be an easy way to increase your protein.如果你喜欢吃鸡蛋,那么它们是将是补充蛋白的简单途径。

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