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 cel l gene expression are not known. We studied the in vitro effects of he at shock on the expression of several genes important to alveolar type II cells. Prior induction of heat shock transiently inhibited cytokin e-mediated inducible nitric oxide synthase gene expression and cytokin e-mediated manganese-superoxide dismutase mRNA expression in murine lu ng epithelium. In contrast, heat shock had no effect on expression of surfactant protein (SP) A or B mRNA, or SP-B peptide synthesis. Cell s urvival studies indicated that the inhibitory effects were not seconda ry to cytotoxicity. Previous heat shock also modestly enhanced the abi lity of cells to withstand oxidant stress. We conclude that in vitro h eat shock has selective and transient inhibitory effects on alveolar t ype II cell gene expression. Transient inhibition of cytokine-inducibl e genes, with concomitant conservation of genes required for normal re spiratory function (SP) may explain, in part, the mechanism by which h eat shock protects during acute lung injury.