Department of Microbial Diseases, UCL-Eastman Dental Institute, University College London, 256 Gray's Inn Rd., London, WC1X 8LD, UK.
J Leukoc Biol. 2010 Sep;88(3):445-62. doi: 10.1189/jlb.1209779. Epub 2010 May 5.
This review critically examines the hypothesis that molecular chaperones and protein-folding catalysts from prokaryotes and eukaryotes can be secreted by cells and function as intercellular signals, principally but not exclusively, for leukocytes. A growing number of molecular chaperones have been reported to function as ligands for selected receptors and/or receptors for specific ligands. Molecular chaperones initially appeared to act primarily as stimulatory signals for leukocytes and thus, were seen as proinflammatory mediators. However, evidence is now emerging that molecular chaperones can have anti-inflammatory actions or, depending on the protein and concentration, anti- and proinflammatory functions. Recasting the original hypothesis, we propose that molecular chaperones and protein-folding catalysts are "moonlighting" proteins that function as homeostatic immune regulators but may also under certain circumstances, contribute to tissue pathology. One of the key issues in the field of molecular chaperone biology relates to the role of microbial contaminants in their signaling activity; this too will be evaluated critically. The most fascinating aspect of molecular chaperones probably relates to evidence for their therapeutic potential in human disease, and ongoing studies are evaluating this potential in a range of clinical settings.
这篇综述批判性地考察了这样一个假设，即原核生物和真核生物的分子伴侣和蛋白质折叠催化剂可以被细胞分泌，并作为细胞间信号发挥作用，主要但不限于白细胞。越来越多的分子伴侣被报道作为特定受体的配体和/或特定配体的受体发挥作用。最初，分子伴侣主要作为白细胞的刺激信号，因此被视为促炎介质。然而，现在有证据表明，分子伴侣可以发挥抗炎作用，或者根据蛋白质和浓度的不同，发挥抗炎和促炎作用。重新考虑最初的假设，我们提出分子伴侣和蛋白质折叠催化剂是“兼职”蛋白质，它们作为体内平衡的免疫调节剂发挥作用，但在某些情况下也可能导致组织病理学。分子伴侣生物学领域的一个关键问题涉及微生物污染物在其信号活性中的作用；这也将受到批判性评估。分子伴侣最吸引人的方面可能与它们在人类疾病中的治疗潜力有关，正在进行的研究正在评估它们在一系列临床环境中的这种潜力。
