Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, D-40225 Düsseldorf, Germany.
West German Center of Diabetes and Health, Düsseldorf Catholic Hospital Group, D-40591 Düsseldorf, Germany.
J Diabetes Res. 2018 Dec 9;2018:4834673. doi: 10.1155/2018/4834673. eCollection 2018.
Heat shock proteins (Hsp) act as intracellular chaperones and in addition are used as adjuvant in vaccines of peptides complexed with recombinant Hsp. By interacting with autologous peptides, Hsp may promote the induction of autoimmune reactivity.
Here, we analysed whether the effect of Hsp on macrophages is modulated by insulin peptides known to interact with Hsp.
Combinations of the 70 kDa Hsp DnaK with peptide B11-23 from the core region of the proinsulin B-chain induced the release of the inflammatory mediators interleukin-6, tumor necrosis factor , and interleukin-1 from cells of human and murine macrophage lines. In parallel, there was high-affinity binding of B11-23 to DnaK. DnaK mixed with peptides from other regions of the insulin molecule did not stimulate cytokine secretion. DnaK alone induced little cytokine production, and peptides alone induced none.
The macrophage-stimulating potential of Hsp70 family proteins when combined with the proinsulin B-chain peptide B11-23 may contribute to the immunodominance of this peptide in the development of beta cell-directed autoimmunity in type 1 diabetes.
热休克蛋白（Hsp）作为细胞内伴侣蛋白发挥作用，此外还可作为与重组 Hsp 复合的肽疫苗的佐剂。通过与自身肽相互作用，Hsp 可能促进自身免疫反应的诱导。
在此，我们分析了与 Hsp 相互作用的胰岛素肽是否会调节 Hsp 对巨噬细胞的作用。
与来自前胰岛素 B 链核心区域的肽 B11-23 组合的 70kDa Hsp DnaK 诱导人源和鼠源巨噬细胞系细胞释放炎症介质白细胞介素-6、肿瘤坏死因子-α 和白细胞介素-1。同时，B11-23 与 DnaK 具有高亲和力结合。DnaK 与胰岛素分子其他区域的肽混合后不会刺激细胞因子分泌。DnaK 本身诱导的细胞因子产生很少，而肽本身则不诱导产生。
当与前胰岛素 B 链肽 B11-23 结合时，Hsp70 家族蛋白的巨噬细胞刺激潜力可能有助于该肽在 1 型糖尿病中β 细胞靶向自身免疫的发展中成为免疫优势肽。
