Chaperones in Sterile Inflammation and Injury

  • Asmita Choudhury
  • Pranoti MandrekarEmail author
Part of the Heat Shock Proteins book series (HESP, volume 16)


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.


Chaperones DAMPs Exosome Heat shock factor 1 Heat shock proteins Inflammation 







Activator protein-1


Antigen presenting cells


Cell division cycle-37


CpG-containing oligodeoxynuceotide


Cytotoxic T lymphocyte


C-X-C motif ligand-10


Damage associated molecular pattern


Dendritic cell


5,5-(N-N-Dimethyl)-amiloride hydrochloride


Extracellular signal-regulated kinases


Hepatoma derived growth factor


Hepatitis C virus


High mobility group box 1


Heat shock element


Heat shock factor 1


Heat shock protein


Heat shock response






IκB kinase




IL-1 receptor-associated kinase


IFN regulatory factor 3


Janus kinase


c-Jun amino-terminal kinases




Mitogen-activated protein kinases


Monocyte chemoattractant protein-1


Major histocompatibility complex


MAP kinase kinase


Matrix metalloproteinases-2


NF-κB essential modulator


Nuclear factor-kappa B


Natural killer


Nod-like receptor


Pathogen associated molecular pattern


Peripheral blood mononuclear cells


Pattern recognition receptor


Rheumatoid arthritis


Receptor for advanced glycation end products


Regulated on activation, normal T cell expressed and secreted


Receptor interacting kinase


RIG-1-like receptor


Reactive nitrogen species


Reactive oxygen species


TAK-1 binding proteins


TGF-β activated kinase 1


TRAF-associated NF-κB activator


TANK-binding kinase 1


Tumor growth factor-beta


Toll/IL-1 receptor


Toll-like receptor


Tumor necrosis factor receptor1


Tumor necrosis factor-alpha


Tumor necrosis factor receptor (TNF-R)-associated factor-6


TRIF related adaptor molecule


Toll/IL- receptor domain containing adaptor inducing IFN-β



This work was supported by grant # RO1 AA17986-01 and RO1 AA25289-01 (to PM) from the National Institute of Alcohol Abuse and Alcoholism, U.S. National Institutes of Health, Bethesda, MD, USA.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA

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