Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview

Abstract

Contribution to a theme issue 'Heat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators' Keywords:Heat shock (stress) proteins, extracellular, immunity Author for correspondence:A. Graham Pockley, PhD e-mail: graham.pockley@ntu.ac.ukHeat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators 2 | P a g e Abstract Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory "danger signals" for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells.The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals / non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining / regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins therefore form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.Heat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators 3 | P a g e 1. Background 'Chance favours the prepared mind ' -Louis Pasteur (1822 -1895 The presence of additional new 'puffs' in the polytene chromosomes of cultured Drosophila larva which were induced following their incubation at an inadvertently high temperature and observed by Ferruccio Ritossa (25 th February 1936 -9 th January 2014) in the early 1960s was unexpected and puzzling. He realised the potential importance of this first evidence that stress can influence gene transcription and induce the synthesis of new proteins, yet found it surprisingly difficult to publish this discovery. It was eventually published in Experientia (1, 2).Ritossa's findings were extended and expanded upon during the next decade and by the mid-to-late 1960s it was clear that exposure of cells containing polytene chromosomes to a variety of environmental stressors resulted in the transcription of novel genes and, presumably, in the synthesi...

Time- and Dose-Dependent Effects of Ionizing Irradiation on the Membrane Expression of Hsp70 on Glioma Cells

“…There is strong evidence that lethal stress which drastically harms tumor cell survival cannot be compensated by cytoprotective repair mechanisms that include the cytosolic overexpression of Hsp70 [31,32]. After lethal stress, Hsp70 can be externalized by dying tumor cells as a danger-associated molecular pattern (DAMP) with the capacity to initiate anti-tumor immune responses [1,2,33]. Hsp70-chaperoned tumor peptides can induce CD8-positive T cell mediated immune responses after cross-presentation of immunogenic tumor antigens on MHC class I molecules [34], whereas peptide-free Hsp70 in the context of pro-inflammatory cytokines, such as IL-2, can augment the cytolytic and migratory capacity of NK cells that recognize and kill remaining therapy-resistant mHsp70-positive tumor cells [16,21].…”

Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults

“…S9C) (11). One of these genes, HSP90B1 , or gp96 – an ER-based chaperone protein implicated in innate and adaptive immune function – is also selected as a predictive gene of antibody response (55, 56).…”

Ovary Proteome Analysis Reveals RH36 Regulates Reproduction via Vitellin Uptake Mediated by HSP70 Protein in Hard Ticks

“…On the one hand, HSP-70 like protein in salivary gland of ticks participates in variable fibrinogenolysis and accelerates engorged quantity upon blood feeding (Vora et al, 2017), immunomodulatory protein RH36 may be dependent on HSP70 protein to modulate tick blood feeding and nutrient supply (Wang et al, 2017). On the other hand, HSP70, as a endoplasmic reticulum chaperone, exhibits both pro-inflammatory and antiinflammatory properties, depending on the context in which they encounter responding immune cells (Pockley and Henderson, 2018). HSP70 may have a synergistic effect with RH36 protein in salivary gland of adult ticks.…”