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HSP70热休克蛋白在炎症性肠病发病机制及治疗中的作用

The Role of HSP70 Heat Shock Proteins in the Pathogenesis and Treatment of Inflammatory Bowel Diseases.

作者信息

Samborski Paweł, Grzymisławski Marian

机构信息

Department of Internal Diseases, Metabolic Diseases and of Dietetics, Clinical Hospital No. 2, Poznan Medical University, Poland.

出版信息

Adv Clin Exp Med. 2015 May-Jun;24(3):525-30. doi: 10.17219/acem/44144.

Abstract

Heat shock proteins (HSPs) represent an important element in the body's defense against various damaging factors. The probably also play an important role in the pathogenesis and treatment of several diseases, including autoimmune pathology and neoplasms. Recently, several investigators have focused their attention on the involvement of the HSP70 protein family in the morbid process of inflammatory bowel diseases (IBD). The HSP70 family of is represented by two distinct forms of protein, the HSP72 protein (also known as the HSP70.1 protein), the expression of which is clearly increased in conditions of stress; and the HSP73 (or HSC73) protein, which manifests stable expression. HSP70 proteins are present in the colorectal epithelium. In patients with inflammatory bowel diseases, their expression in significantly increased during the active stage of the disease. In experimental studies, overexpression of HSP70 was found to prevent the development of inflammatory process in the large intestinal mucosa provoked by various damaging factors. In physiological conditions, various mechanisms are considered to be responsible for an increased expression of HSP70. One of them involves lymphocyte activity and the production of cytokines (mainly IL-2). Another suggested mechanism involves the presence of bacteria in the large intestine, including both physiological flora (Lactobacillus GG, Bacteroides fragilis) and pathogenic bacteria (Salmonella, Escherichia coli). HSP70 expression is probably also increased by physical activity. There is also a potential for pharmacological stimulation of HSP70 expression, linked (for example) to geranylgeranylacetone, polaprezinc and mesalazine. Thus, augmentation of HSP70 expression may become a new element in IBD therapy.

摘要

热休克蛋白(HSPs)是机体抵御各种损伤因素的重要组成部分。它们可能在包括自身免疫性疾病和肿瘤在内的多种疾病的发病机制及治疗中发挥重要作用。最近,一些研究人员将注意力集中在HSP70蛋白家族在炎症性肠病(IBD)发病过程中的作用。HSP70家族由两种不同形式的蛋白质代表,即HSP72蛋白(也称为HSP70.1蛋白),其在应激条件下表达明显增加;以及HSP73(或HSC73)蛋白,其表现为稳定表达。HSP70蛋白存在于结肠上皮中。在炎症性肠病患者中,它们在疾病活动期的表达显著增加。在实验研究中,发现HSP70的过表达可预防各种损伤因素引起的大肠黏膜炎症过程的发展。在生理条件下,多种机制被认为与HSP70表达增加有关。其中之一涉及淋巴细胞活性和细胞因子(主要是IL-2)的产生。另一种推测机制涉及大肠中细菌的存在,包括生理性菌群(嗜酸乳杆菌GG、脆弱拟杆菌)和病原菌(沙门氏菌、大肠杆菌)。体育活动可能也会增加HSP70的表达。此外,还存在通过药物刺激HSP70表达的可能性,例如与香叶基香叶基丙酮、聚普瑞锌和美沙拉嗪有关。因此,增强HSP70表达可能成为IBD治疗的新要素。

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