Detanico T, Rodrigues L, Sabritto A C, Keisermann M, Bauer M E, Zwickey H, Bonorino C
National Jewish Medical & Research Center, Denver, CO, USA.
Clin Exp Immunol. 2004 Feb;135(2):336-42. doi: 10.1111/j.1365-2249.2004.02351.x.
Cytokines are key modulators of the immune responses that take place in the inflamed synovium of arthritis patients. Consequently, substances that can reverse the inflammatory profile of the inflamed joint are potential tools for clinical management of the disease. Mycobacterial heat shock protein 70 (MTBHSP70) has been found to protect rats from experimentally induced arthritis through the induction of interleukin (IL)-10-producing T cells. In this study, we have demonstrated that MTBHSP70 induces IL-10 production in synoviocytes from arthritis patients and peripheral blood monoculear cells (PBMCs) from both patients and healthy controls. IL-10 production was accompanied by a decrease in tumour necrosis factor (TNF)-alpha production by synovial cells. Separation studies showed that the target cells were mainly monocytes. Accordingly, we observed that MTBHSP70 delayed maturation of murine bone marrow-derived dendritic cells. Our results suggest that MTBHSP may act on antigen-presenting cells (APCs) to modulate the cytokine response in arthritis and support an anti-inflammatory role for this protein, suggesting that it may be of therapeutic use in the modulation of arthritis.
细胞因子是关节炎患者炎症滑膜中发生的免疫反应的关键调节因子。因此，能够逆转炎症关节炎症状态的物质是该疾病临床治疗的潜在工具。已发现分枝杆菌热休克蛋白70（MTBHSP70）通过诱导产生白细胞介素（IL）-10的T细胞来保护大鼠免受实验性诱导的关节炎。在本研究中，我们证明MTBHSP70可诱导关节炎患者滑膜细胞以及患者和健康对照者外周血单个核细胞（PBMC）产生IL-10。IL-10的产生伴随着滑膜细胞肿瘤坏死因子（TNF）-α产生的减少。分离研究表明靶细胞主要是单核细胞。因此，我们观察到MTBHSP70延迟了小鼠骨髓来源树突状细胞的成熟。我们的结果表明，MTBHSP可能作用于抗原呈递细胞（APC）以调节关节炎中的细胞因子反应，并支持该蛋白的抗炎作用，表明它可能在关节炎的调节中具有治疗用途。
