THE STRESS-RESPONSE AND THE LUNG

The stress response is a highly conserved cellular defense mechanism d efined by the rapid and specific expression of stress proteins, with c oncomitant transient inhibition of nonstress protein gene expression. The stress proteins mediate cellular and tissue protection against div erse cytotoxic stimuli. Among the many classes of stress proteins, hea t shock protein 70 and heme oxygenase-1 are the best characterized wit h respect to lung biology. A potential role for stress proteins in hum an lung disease is inferred from studies demonstrating stress protein expression in the lungs of patients with cancer, asthma, and acute lun g injury. Several examples of stress protein-mediated cytoprotection e xist in cell and animal models of acute lung injury. Stress protein in duction protects rats against acute lung injury caused by either syste mic administration of endotoxin or intratracheal administration of pho spholipase A(1). In vitro, increased expression of stress proteins pro tects lung cells against endotoxin-mediated apoptosis and oxidant inju ry. The mechanisms of stress response-mediated cytoprotection may invo lve the enzymatic and molecular chaperone properties of stress protein s. Alternatively, the stress response may protect by modulating lung p roinflammatory responses. Data from extrapulmonary systems suggest tha t stress response-associated factors (heat shock protein 70 and heat s hock factor) are directly involved in modulation of proinflammatory ge ne expression. Recent evidence also demonstrates interactions between the stress response and the I-kappa B/nuclear factor-kappa B pathway i n cultured lung cells. Increased understanding about the role of stres s proteins in lung biology may support efforts to selectively increase expression of one or more stress proteins to provide protection again st human acute lung injury.