Abstract
The modulation of the innate immune system has been a significant area of interest in research, as it represents the body’s first line of defense against pathogens. Heat shock proteins (HSPs), particularly small HSP, like HSPB1 (HSP27), are emerging as potent therapeutic options for preventing and managing inflammatory conditions due to their ability to modulate the immune system. Studies have shown that exogenous HSPB1 (exHSPB1) can stimulate macrophages and other immune cells to initiate an inflammatory response, offering several potential advantages over existing treatments; and given the strong anti-inflammatory effects that has exHSPB1 upon macrophage stimulation, exHSPB1 could be used as a powerful tool in managing and mitigating inflammatory diseases.
The results obtained demonstrated that exHSPB1 can induce the secretion of both pro-inflammatory and anti-inflammatory cytokines in THP-1 macrophages. Furthermore, preincubation with specific TLR blocking peptides confirmed the presence of the TLRs on the surface of macrophages and showed that exHSPB1- induced cytokine secretion depends on TLR interaction with external stimuli. Additionally, the intracellular signaling proteins MYD88, MAPK P38, and NF-κβ P65 were found to be activated within the exHSPB1 treated cells, with NF-κβ gene expression significantly upregulated.
Given these results, exHSPB1 proved to be a promising therapeutic agent for controlling inflammation and could be a valuable agent in the development of treatments. For example, exHSPB1 can enhance the activity of immune cells like macrophages and T cells in inflammatory diseases or cancer.
Keywords
Cytokines, HSPB1, Immune response, THP-1, TLRs