Selective and transient in vitro effects of heat shock on alveolar
type ii cell gene expression.
Wong, Hector R., Marnie Ryan, Sarah Gebb, and Jonathan R. Wisp.
Divisions of Critical Care Medicine1 and Pulmonary Biology,
Children's Hospital Medical Center, Cincinnati, OH 45229
APStracts 3:0162L, 1996.
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. Prior 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 (SPs) may explain, in part, the mechanism by which heat
shock protects during acute lung injury.
Received 19 March 1996; accepted in final form 4 September 1996.
APS Manuscript Number L86-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996