Department of Biochemistry, University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Cell Stress Chaperones. 2010 Sep;15(5):555-66. doi: 10.1007/s12192-010-0168-z. Epub 2010 Feb 2.
Recent research on the heat shock proteins (Hsps) in chronic inflammatory diseases indicates that Hsps may have disease-suppressive activities. Our aim was to characterize immune response directed to bacterial (DnaJ) and human Hsp40s in patients with rheumatoid arthritis (RA). We found elevated levels of anti-DnaJ, anti-Hdj2, and anti-Hdj3 (but not ant-Hdj1) serum antibodies in the RA patients (P < or = 0.001) compared to healthy controls. In peripheral blood mononuclear cells (PBMCs) culture, all tested Hsp40 proteins significantly inhibited the divisions of CD4+ and CD8+ T cells of the RA patients but not those of the controls. Both DnaJ and Hdj2 stimulated secretion of the main anti-inflammatory cytokine IL-10 by PBMCs of the RA patients (P < 0.05), and of IL-6 by PBMCs of the RA (P < 0.001) and control (P < 0.01) groups. DnaJ reduced TNFalpha secretion (P < 0.05) by both groups of PBMCs. Our results show for the first time that the RA patients have an increased humoral response to human Hsp40 proteins Hdj2 and Hdj3. This is also the first description of immunomodulatory effect of human Hsp40s on T cells and cytokine secretion in RA, suggesting that Hsp40s act as natural anti-inflammatory agents in RA.
最近关于热休克蛋白（Hsps）在慢性炎症性疾病中的研究表明，Hsps 可能具有抑制疾病的活性。我们的目的是研究类风湿关节炎（RA）患者针对细菌（DnaJ）和人 HSP40 的免疫反应。我们发现 RA 患者血清中抗 DnaJ、抗 Hdj2 和抗 Hdj3（而非抗 Hdj1）的水平升高（P<0.001）。在体外培养的外周血单核细胞（PBMC）中，所有测试的 HSP40 蛋白均显著抑制 RA 患者的 CD4+和 CD8+T 细胞分裂，但对对照组无此作用。DnaJ 和 Hdj2 刺激 RA 患者 PBMC 分泌主要抗炎细胞因子 IL-10（P<0.05），并刺激 RA（P<0.001）和对照组（P<0.01）PBMC 分泌 IL-6。DnaJ 减少两组 PBMC 分泌 TNFalpha（P<0.05）。我们的结果首次表明，RA 患者对人 HSP40 蛋白 Hdj2 和 Hdj3 的体液反应增强。这也是人 HSP40 对 RA 中 T 细胞和细胞因子分泌的免疫调节作用的首次描述，表明 HSP40 在 RA 中充当天然抗炎剂。
