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

Abstract

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.

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

“…Previous studies have shown that HSPA1A/HSPA1B and TRIM15 play roles in the pathogenesis of psoriasis ( 71 , 91 ). HSPA1A and HSPA1B are heat shock proteins that regulate the secretion of TNF-α, IL-1β and IL-10 from monocytes ( 133 ). TRIM15, on the other hand, stimulates TNF-α and is involved in the TNF-α/NF-κB pathway, contributing to the inflammatory response ( 91 ).…”

Bioinformatic Identification of Signaling Pathways and Hub Genes in Vascular Dementia

“…Research suggests that HSPA1A regulates the JNK/p38 pathway within the MAPK signaling pathway and can inhibit apoptosis induced by this pathway [36]. HSPB1, a potential antiinflammatory gene, represents a compensatory response to pro-inflammatory reactions [37]. PRPF4B, a kinase belonging to the Cell Division Cycle-like Kinase (CLK) protein kinase family [38].…”

Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target

“…It engages monocytes via TLR2/4 in a CD14-dependent manner, stimulating the myeloid differentiation primary response gene 88 (MyD88)/interleukin-1 receptor-associated kinase (IRAK)/NF-kB signaling cascade to promote the production of pro-inflammatory cytokines (103). Other receptors, including CD40, CD36, and CD11b, were also found to mediate those effects, partly via the p38/MAPK pathway (104,105). Subsequently, an increasing body of evidence indicated that eHSP70, contrary to its well-established oncogenic functions in other aspects of cancer biology, plays a paradoxical role in immune responses against cancer cells (Figure 3).…”