热休克蛋白:炎症性疾病的治疗观点。

IF 4.2 Q3 Pharmacology, Toxicology and Pharmaceutics
R. Khandia, A. Munjal, Hafiz M.N. Iqbal, K. Dhama
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引用次数: 51

摘要

背景:热休克蛋白(HSPs)是存在于所有生物王国中高度保守的蛋白。这些蛋白在应激条件下表达,以保护细胞免受损伤。应激诱导的蛋白质变性是通过重折叠和重塑来纠正的。这些是细胞内蛋白,但也可能存在于创伤、自身免疫性疾病和炎症性疾病患者的血清等细胞外液中。事实上,在大多数炎症性疾病中,对热休克蛋白的免疫反应是发达的。目的:本综述加速了热休克蛋白在炎症过程和相关疾病中的作用,主要是在HSP70和HSP90的背景下。方法从Medline、Pubmed、Pubmed Central、Science Direct等科学数据库中对热敏感蛋白及其在炎症过程中的作用的文献和专利进行全面调查;检索到的信息已被编译和分析。结果shsps通过产生抗炎细胞因子调节慢性炎性疾病的炎症过程。HSPs介导的IL10表达通过TLR2和tlr4依赖机制参与抗炎作用。坏死坏死是一种不依赖caspase的程序性凋亡,在多种炎症性疾病的进展中起重要作用,其主要成分MLKL和RIPK-1是HSP的客户。坏死性上睑下垂还涉及细胞外环境中几种损伤相关分子模式(DAMPs)的暴露,包括热休克蛋白(HSPs),导致炎症。内吞的或细胞内的HSP70,由MHC-II分子呈递,在缺乏适当的协同刺激的情况下,它导致耐受性或调节性T细胞(Tregs)反应的扩大,这些反应通过产生抗炎细胞因子、抑制或杀死效应T细胞或使APC进入耐受性状态而具有炎症抑制活性。热休克蛋白诱导的treg在对抗自身免疫和炎症中发挥重要作用。结论本文综述了炎症的原因,并阐述了不同热休克蛋白对炎症性肠病(IBD)、肠道炎症、动脉粥样硬化、类风湿性关节炎(RA)、多发性硬化症等炎症疾病的影响。热休克蛋白在处理炎症性疾病中的重要性也已在最近的专利中描述。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Heat Shock Proteins: Therapeutic Perspectives in Inflammatory Disorders.
BACKGROUND Heat shock proteins (HSPs) are highly conserved proteins present in all kingdoms of organisms. These are expressed under stress conditions in order to protect the cells from injuries. The stress induced protein denaturation is rectified by refolding and remodelling. These are intracellular proteins but can be present in extracellular fluid like serum of the patients suffering from trauma, autoimmune and inflammatory disorders. Virtually in most inflammatory diseases, immune response towards HSPs is developed. OBJECTIVE The present review expedites the role of HSPs in inflammatory process and associated disorders, mainly in context to HSP70 and HSP90. METHOD Commencing a thorough survey of the literature and patents available on HSPs and their role in the process of inflammation, from the authentic published resources available on Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases; the information retrieved has been compiled and analyzed. RESULTS HSPs modulate the process of inflammation by producing anti-inflammatory cytokines in chronic inflammatory disease. HSPs mediated expression of IL10 contributes in anti-inflammatory role via TLR2 and TLR4-dependent mechanisms. Necroptosis, a caspase independent programmed apoptosis plays an important role in progression of several inflammatory disorders and its major components MLKL and RIPK-1 are the clients of HSP. Necroptosis is also involved in exposure of several damageassociated molecular patterns (DAMPs) including HSPs in extracellular environment leading to inflammation. Endocytosed or intracellular HSP70, is presented by MHC-II molecules and in absence of proper co stimulation, it lead to expansion of tolerogenic or regulatory T cells (Tregs) responses, which have inflammation suppressive activity by virtue of production of anti-inflammatory cytokines, suppression or killing of effector T cells or bringing the APC into tolerogenic state. HSP induced Tregs play an important role in combating autoimmunity and inflammation. CONCLUSION Present review gives an insight towards the cause of inflammation and an account of different HSPs contributing various inflammatory disorders viz. inflammatory bowel disease (IBD), intestinal inflammation, atherosclerosis, rheumatoid arthritis (RA), multiple sclerosis etc. The importance of HSPs in handling inflammatory disorders has been depicted in recent patents also.
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来源期刊
CiteScore
3.90
自引率
0.00%
发文量
0
期刊介绍: Recent Patents on Inflammation & Allergy Drug Discovery publishes review articles by experts on recent patents in the field of inflammation and allergy drug discovery e.g. on novel bioactive compounds, analogs and targets. A selection of important and recent patents in the field is also included in the journal. The journal is essential reading for all researchers involved in inflammation and allergy drug design and discovery.
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