外源热休克蛋白 HSPA1A 和 HSPB1 调节单核细胞的 TNF-α、IL-1β 和 IL-10 分泌,FEBS Open Bio

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外源热休克蛋白 HSPA1A 和 HSPB1 调节单核细胞的 TNF-α、IL-1β 和 IL-10 分泌
FEBS Open Bio ( IF 2.8 ) Pub Date : 2023-08-15 , DOI: 10.1002/2211-5463.13695
Emmanuel Ogbodo ₁ , Francesco Michelangeli ₂ , John H H Williams ₃

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内源性分子，例如热休克蛋白（HSP），在释放到细胞外环境以响应细胞应激时可以充当危险信号，从而引发细胞因子分泌等免疫反应。还有一些建议认为，外源热休克蛋白被脂多糖 (LPS) 污染可能是造成这些影响的原因。本研究探讨了外源性 HSPA1A 和 HSPB1 对免疫细胞激活和细胞因子分泌的影响，这些细胞因子参与炎症反应。为了研究外源性 HSP 是否可以直接激活细胞因子分泌，用外源性 HSPA1A 或 HSPB1 处理幼稚 U937 细胞、分化的 U937 细胞和外周血单核细胞 (PBMC)，然后分泌 IL-1β、TNF-α 和 IL-10。通过ELISA测量。两种 HSP 都能诱导初始 U937 细胞中 IL-10 分泌的剂量依赖性增加，并且在分化的 U937 细胞和 PBMC 中也观察到剂量依赖性 IL-1β、TNF-α 和 IL-10 分泌。我们还观察到 CD14 影响细胞响应外源 HSP 治疗的 IL-1β、TNF-α 和 IL-10 的分泌水平。此外，HSPA1A 和 HSPB1 与 CD14、CD36 和 CD11b 细胞外受体蛋白相互作用。本研究中使用的几种方法表明，HSP 诱导的细胞因子分泌在很大程度上独立于样品中的任何污染性 LPS。

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Exogenous heat shock proteins HSPA1A and HSPB1 regulate TNF-α, IL-1β and IL-10 secretion from monocytic cells

Endogenous molecules, such as heat shock proteins (HSP), can function as danger signals when released into the extracellular environment in response to cell stress, where they elicit an immune response such as cytokine secretion. There has also been some suggestion that contamination of exogenous HSPs with lipopolysaccharide (LPS) may be responsible for these effects. This study investigates the effects of exogenous HSPA1A and HSPB1 on the activation of immune cells and the resulting secretion of cytokines, which are involved in inflammatory responses. To address whether exogenous HSPs can directly activate cytokine secretion, naïve U937 cells, differentiated U937 cells and peripheral blood mononuclear cells (PBMCs) were treated with either exogenously applied HSPA1A or HSPB1 and then secreted IL-1β, TNF-α and IL-10 were measured by ELISA. Both HSPs were able to induce a dose-dependent increase in IL-10 secretion from naïve U937 cells and dose-dependent IL-1β, TNF-α and IL-10 secretion were also observed in differentiated U937 cells and PBMCs. We also observed that CD14 affects the secretion levels of IL-1β, TNF-α and IL-10 from cells in response to exogenous HSP treatment. In addition, HSPA1A and HSPB1 were shown to interact with CD14, CD36 and CD11b extracellular receptor proteins. Several approaches used in this study indicate that HSP-induced cytokine secretion is largely independent of any contaminating LPS in the samples.

更新日期：2023-08-15

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