The stress response and the lung

Abstract

The stress response is a highly conserved cellular defense mechanism defined by the rapid and specific expression of stress proteins, with concomitant transient inhibition of nonstress protein gene expression. The stress proteins mediate cellular and tissue protection against diverse cytotoxic stimuli. Among the many classes of stress proteins, heat shock protein 70 and heme oxygenase-1 are the best characterized with respect to lung biology. A potential role for stress proteins in human lung disease is inferred from studies demonstrating stress protein expression in the lungs of patients with cancer, asthma, and acute lung injury. Several examples of stress protein-mediated cytoprotection exist in cell and animal models of acute lung injury. Stress protein induction protects rats against acute lung injury caused by either systemic administration of endotoxin or intratracheal administration of phospholipase A1. In vitro, increased expression of stress proteins protects lung cells against endotoxin-mediated apoptosis and oxidant injury. The mechanisms of stress response-mediated cytoprotection may involve the enzymatic and molecular chaperone properties of stress proteins. Alternatively, the stress response may protect by modulating lung proinflammatory responses. Data from extrapulmonary systems suggest that stress response-associated factors (heat shock protein 70 and heat shock factor) are directly involved in modulation of proinflammatory gene expression. Recent evidence also demonstrates interactions between the stress response and the I-kappa B/nuclear factor-kappa B pathway in cultured lung cells. Increased understanding about the role of stress proteins in lung biology may support efforts to selectively increase expression of one or more stress proteins to provide protection against human acute lung injury.

Association of hsp70-2 and hsp-hom gene polymorphisms with risk of acute high-altitude illness in a Chinese population

“…Previous studies suggest that Hsp70 can protect different organs from oxidative damages resulting from ischemia/ reperfusion and may play an autoprotective role in asthma and lung injury (Bonay et al 1994;Wong and Wispe 1997;Bertorelli et al 1998;Tong and Luo 2002). The HSP70 family proteins may be the most predominant and particularly interesting group of proteins involved in the major histocompatibility complex in disease susceptibility (Favatier et al 1997).…”

Heat shock response and acute lung injury☆

“…Hsp70 expression 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 (128). More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that stress proteins have an important cytoprotective role during lung inflammation and injury (128).…”

“…More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that stress proteins have an important cytoprotective role during lung inflammation and injury (128). For example, induction of the stress response by either thermal stress or sodium arsenite attenuates LPSmediated apoptosis in cultured sheep pulmonary artery endothelial cells (8), perhaps via an anti-oxidant mechanism, as induction of the stress response was temporally associated with a reduction in LPS-mediated superoxide anion production.…”

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

“…T he role of heat shock proteins as an endogenous protective mechanism is well established (1,2). One group of these highly conserved proteins is constitutively expressed, aiding in the assembly, stabilization, and translocation of cellular proteins.…”