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.
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