Expression of inducible nitric oxide synthase in cultured rat
pulmonary artery smooth muscle cells is inhibited by the heat shock
response.
Wong, Hector R., Jonathan D. Finder, Karla Wasserloos, and Bruce R.
Pitt.
Departments of Anesthesiology/Critical Care Medicine, Division of
Pediatric Critical Care Medicine, Pediatrics, and Pharmacology,
University of Pittsburgh School of Medicine, Pittsburgh, PA 15217
APStracts 2:0149L, 1995.
The heat shock response is a highly conserved stress response known to
alter patterns of gene expression in many cell types. We hypothesized
that interleukin-1 (IL-1)-mediated inducible nitric oxide synthase
(iNOS) gene expression would be inhibited following induction of the
heat shock response in cultured rat pulmonary artery smooth muscle
cells (RPASMC). Exposure of RPASMC to sodium arsenite or heat lead to
expression of heat shock protein-70 (HSP-70) in a time- and
concentration-dependent manner. Prior induction of the heat shock
response inhibited IL-1-mediated iNOS gene expression in a time- and
dose-dependent manner. The inhibitory effects were not due to
cytotoxicity since cell viability was not affected by either sodium
arsenite, heat, IL-1, or their combination. Transcriptional analysis
via transient transfection of the murine macrophage iNOS promoter (
-1592 and -367 bp), upstream from the reporter gene luciferase,
revealed that the heat shock response did not affect IL-1[beta]
-mediated promoter activation as measured by luciferase activity. We
conclude that induction of the heat shock response inhibits IL-1
-mediated iNOS gene expression in cultured RPASMC.
Received 13 December 1994; accepted in final form 20 June 1995.
APS Manuscript Number L354-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.