A synthetic 10‐kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis
A synthetic 10‐kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis
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DOI：
10.1111/j.1365-2249.1996.tb08291.x
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发表时间：
1996-03
影响因子：
4.6
通讯作者：
S. Ragno;V. Winrow;Paolo Mascagni;P. Lucietto;F. D. Pierro;Christopher Morris;D. R. Blake
中科院分区：
文献类型：
--
作者：
S. Ragno;V. Winrow;Paolo Mascagni;P. Lucietto;F. D. Pierro;Christopher Morris;D. R. Blake
热休克蛋白hsp 10是结核分枝杆菌（Mycobacterium tuberculosis，Mtb）中的一种丰富的蛋白质，其核苷酸序列编码99个氨基酸，分子量为10±7kD。该序列在遗传学上是保守的，由大肠杆菌的GroES同源物代表。Hsp 10和GroES是分子伴侣蛋白伴侣蛋白10家族的成员，GroES是GroEL（伴侣蛋白60家族的成员和分枝杆菌hsp 65的大肠杆菌同源物）的最佳活性所必需的。由于hsp65与实验性和人类类风湿性关节炎有关，我们的目的是评估其辅伴侣蛋白hsp10在实验性关节炎中的免疫调节作用。我们的研究结果表明，当在疾病诱导后但在关节受累发生前给药时，分枝杆菌hsp10的水溶液延迟了啮齿动物佐剂诱导关节炎的发作和严重程度。这种生物活性对结核分枝杆菌的hsp10是特异性的，因为GroES和大鼠同源物都无效。使用合成的hsp10片段，活性定位于分子的N末端区域。对分枝杆菌hsp10和hsp65的循环抗体水平的评估表明，所有关节炎大鼠对hsp10和hsp65的抗体水平均增加：与未治疗的关节炎对照组相比，hsp10治疗的大鼠不仅对hsp10而且对hsp65的体液应答进一步升高。这是第一份关于分枝杆菌hsp10在实验性关节炎中的免疫调节活性的报告，并显示出这种辅助分子伴侣在病理生理学情况下的潜在作用。
The heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10±7kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp 10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroES is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co‐chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant‐induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES nor the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N‐terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased litres to both hsp10 and hsp65: hsp10‐treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co‐chaperonin in pathophysiological situations.