Selective and transient in vitro effects of heat shock on alveolar type II cell gene expression

The heat shock response is a highly conserved stress response that can transiently inhibit non-heat shock protein gene expression. Although heat shock protects against acute lung injury, its effects on lung cell gene expression are not known. We studied the in vitro effects of heat shock on the expression of several genes important to alveolar type II cells. Prior induction of heat shock transiently inhibited cytokine-mediated inducible nitric oxide synthase gene expression and cytokine-mediated manganese-superoxide dismutase mRNA expression in murine lung epithelium. In contrast, heat shock had no effect on expression of surfactant protein (SP) A or B mRNA, or SP-B peptide synthesis. Cell survival studies indicated that the inhibitory effects were not secondary to cytotoxicity. Previous heat shock also modestly enhanced the ability of cells to withstand oxidant stress. We conclude that in vitro heat shock has selective and transient inhibitory effects on alveolar type II cell gene expression. Transient inhibition of cytokine-inducible genes, with concomitant conservation of genes required for normal respiratory function (SP) may explain, in part, the mechanism by which heat shock protects during acute lung injury.