Heat shock response and acute lung injury☆

Abstract

All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury.

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS

“…HSP 70 genes are among the most highly heatinducible mammalian genes known. In animal and cellular models of thermal stress, intracellular expression of these genes correlates with the acquisition of thermotolerance and cross-resistance to a variety of nonthermal stimuli (Wheeler and Wong 2007). Furthermore, release of HSP 70 by stressed cells into the extracellular space may serve as an activating signal to the innate immunity system (Wheeler and Wong 2007).…”

“…In animal and cellular models of thermal stress, intracellular expression of these genes correlates with the acquisition of thermotolerance and cross-resistance to a variety of nonthermal stimuli (Wheeler and Wong 2007). Furthermore, release of HSP 70 by stressed cells into the extracellular space may serve as an activating signal to the innate immunity system (Wheeler and Wong 2007). The present findings suggest the interesting possibility that inflammatory mediators or other humoral factors unique to sepsis might somehow blunt the temperature-dependent expression response of HSP 70 family genes.…”

Hsp72 Induces Inflammation and Regulates Cytokine Production in Airway Epithelium through a TLR4- and NF-κB-Dependent Mechanism

“…Furthermore, that release has been shown to involve an exosome-dependent, nonclassical protein secretory pathway in human PBMC and tumor cells (47,48). Although both active and necrotic cell release mechanisms may be involved in extracellular Hsp72 signaling, the possibility of active release allows for a markedly inducible response to a variety of insults, providing amplification of a local danger signal to neighboring cells (49).…”

Heat-induced transcription of diphtheria toxin A or its variants, CRM176 and CRM197: implications for pancreatic cancer gene therapy

“…HSPs, highly conserved cytoprotective proteins found in all animal species, have a fundamental function in protein folding, transport, translocation, degradation and assembly; 29 their transcription is triggered when cytoplasmic heat shock factor monomers have been trimerized, translocated into the nucleus and recognized by specific promoter motifs, the so-called heat shock elements (HSEs). 30 Although HSP expression was originally observed in cells after acute stress, 31 several members of this family are constitutively expressed; 30,32,33 however, HSPs with inducible rather than constitutive expression seem more suitable for gene therapy applications, as inducible expression can be manipulated.…”