Chaperones in Sterile Inflammation and Injury

Abstract

Heat shock proteins (Hsp) are highly conserved proteins and their expression increases in response to stress stimuli for the maintenance of cellular homeostasis. Cellular stress conditions like hypoxia, change in pH, and metabolic changes are typically associated with upregulation of HSP. In addition to their traditional role of protein refolding or degradation during maintenance of homeostasis, Hsp also acts as key modulators of innate and adaptive immune pathways and play an important role in inflammation and host defense mechanisms. Several pathological conditions such as chronic inflammatory diseases and cancer are typically marked with an elevated expression of HSP. Increasing evidence demonstrates that Hsp can be secreted in the extracellular milieu during disease conditions. These proteins are released into the extracellular spaces either by necrotic cell death or by active secretion via exosomes. Exosomes containing Hsp can communicate and release exosomal contents to elicit immune cell activation. Thus, increased levels of Hsp can be considered as a danger signal both intracellularly, for its ability to chaperone inflammatory signaling molecules as well as extracellularly, for eliciting the activation of immune cells via exosomal communications. This chapter summarizes the chaperone role of HSP in serving as regulators of the immune response in chronic disease conditions.