Routsias John G, Tzioufas Athanasios G
Department of Pathophysiology, School of Medicine, University of Athens, 11527 Athens, Greece.
Ann N Y Acad Sci. 2006 Nov;1088:52-64. doi: 10.1196/annals.1366.029.
Heat-shock or stress proteins (HSPs) are intracellular molecules that are expressed under cellular stress and have housekeeping and cytoprotective functions. Many of them act also as molecular chaperones, assisting the correct folding, stabilization, and translocation of proteins. In pathological situations, such as necrotic cell death, they can be released into the extracellular environment complexed with intact or fragmented cellular proteins. Evidence is now accumulating to indicate that, under certain circumstances, these complexes can contribute to induction of autoimmunity by receptor-mediated activation of the innate immune response (signaling the "danger") and by participation in the presentation of autoantigens for the adaptive immune response (acting as natural adjuvants). In addition, the conservation of HSPs through prokaryotes and eukaryotes, together with the increased production of host and microbial HSPs at the site of infection, has led to the proposition that these proteins may provide a link between infection and autoimmunity. This review outlines the mechanisms for the potential involvement of chaperones in the induction of autoimmune disease.
热休克蛋白或应激蛋白（HSPs）是细胞内分子，在细胞应激时表达，具有看家及细胞保护功能。它们中的许多还充当分子伴侣，协助蛋白质正确折叠、稳定及转运。在诸如坏死性细胞死亡等病理情况下，它们可与完整或片段化的细胞蛋白复合后释放到细胞外环境中。现在越来越多的证据表明，在某些情况下，这些复合物可通过受体介导的固有免疫反应激活（发出“危险”信号）以及参与自身抗原向适应性免疫反应的呈递（充当天然佐剂）来促进自身免疫的诱导。此外，热休克蛋白在原核生物和真核生物中的保守性，以及宿主和微生物热休克蛋白在感染部位的产量增加，使得人们提出这些蛋白质可能在感染和自身免疫之间提供了一种联系。本综述概述了分子伴侣潜在参与自身免疫性疾病诱导的机制。
