Ragno S, Winrow V R, Mascagni P, Lucietto P, Di Pierro F, Morris C J, Blake D R
The Inflammation Research Group, ARC Bone & Joint Research Unit, The London Hospital Medical College, London, UK.
Clin Exp Immunol. 1996 Mar;103(3):384-90. doi: 10.1111/j.1365-2249.1996.tb08291.x.
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 10.7 kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp10 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 not 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 titres 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.
热休克蛋白hsp10是结核分枝杆菌（Mtb）中一种丰富的蛋白质，其核苷酸序列编码一种由99个氨基酸组成、分子量为10.7 kD的蛋白质。该序列在系统发育上是保守的，由大肠杆菌的GroES同源物代表。Hsp10和GroES是分子伴侣伴侣蛋白10家族的成员，而GroES对于伴侣蛋白60家族成员GroEL的最佳活性是必需的，GroEL是分枝杆菌hsp65的大肠杆菌同源物。由于hsp65与实验性和人类类风湿性关节炎均有关联，我们旨在评估其共伴侣蛋白hsp10在实验性关节炎中的免疫调节作用。我们的结果表明，在疾病诱导后但关节受累之前给予分枝杆菌hsp10的水溶液，可延迟啮齿动物佐剂诱导性关节炎的发病和严重程度。这种生物活性对Mtb的hsp10具有特异性，因为GroES和大鼠同源物均无效。使用合成的hsp10片段，该活性定位于分子的N端区域。对分枝杆菌hsp10和hsp65的循环抗体水平评估表明，所有关节炎大鼠对hsp10和hsp65的滴度均升高：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的这种体液反应进一步升高。这是关于分枝杆菌hsp10在实验性关节炎中的免疫调节活性的首次报道，并展示了这种共伴侣蛋白在病理生理情况下的潜在作用。
