Department of Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
J Biol Chem. 2012 Apr 6;287(15):12387-94. doi: 10.1074/jbc.M111.307579. Epub 2012 Feb 13.
Heat shock protein 70 (Hsp70) has gained a lot of attention in the past decade due to its potential immunoregulatory functions. Some of the described proinflammatory functions of Hsp70 became controversial as they were based on recombinant Hsp70 proteins specimens, which were later shown to be endotoxin-contaminated. In this study we used low endotoxin inducible Hsp70 (also known as Hsp72, HSPA1A), and we observed that after a 24-h incubation of monocyte-derived immature dendritic cells (mo-iDCs) with 20 μg/ml of low endotoxin Hsp70, their ability to stimulate allogenic T cells was reduced. Interestingly, low endotoxin Hsp70 also significantly reduced T cell responses when they were simulated with either IL-2 or phytohemagglutinin, therefore showing that Hsp70 could alter T cell responses independently from its effect on mo-iDCs. We also reported a greater response of Hsp70 treatment when activated versus nonactivated T cells were used. This effect of Hsp70 was similar for all tested populations of T cells that included CD3(+), CD4(+), or CD8(+). Taken together, our observations strongly suggest that Hsp70 might dampen, rather than provoke, T cell-mediated inflammatory reactions in many clinical conditions where up-regulation of Hsp70 is observed.
热休克蛋白 70（Hsp70）在过去十年中因其潜在的免疫调节功能而受到广泛关注。由于其描述的一些促炎功能基于重组 Hsp70 蛋白标本，后来发现这些标本被内毒素污染，因此这些功能受到了争议。在本研究中，我们使用低内毒素诱导的 Hsp70（也称为 Hsp72、HSPA1A），我们观察到单核细胞来源的未成熟树突状细胞（mo-iDCs）在与 20 μg/ml 的低内毒素 Hsp70 孵育 24 小时后，其刺激同种异体 T 细胞的能力降低。有趣的是，低内毒素 Hsp70 在用白细胞介素 2 或植物血球凝集素刺激时也显著降低了 T 细胞反应，表明 Hsp70 可以独立于其对 mo-iDCs 的影响来改变 T 细胞反应。我们还报告说，当使用激活的 T 细胞而非非激活的 T 细胞进行治疗时，Hsp70 的反应更大。这种 Hsp70 的作用对于包括 CD3(+)、CD4(+)或 CD8(+)在内的所有测试 T 细胞群体都是相似的。综上所述，我们的观察结果强烈表明，在许多观察到 Hsp70 上调的临床情况下，Hsp70 可能会抑制而不是引发 T 细胞介导的炎症反应。
