EXPRESSION OF INOS IN CULTURED RAT PULMONARY-ARTERY SMOOTH-MUSCLE CELLS IS INHIBITED BY THE HEAT-SHOCK RESPONSE

1995.--The heat shock response is a highly conserved stress response k nown to alter patterns of gene expression in many cell. types. We hypo thesized that interleukin-lp (IL-1 beta)-mediated inducible nitric oxi de synthase (iNOS) gene expression would be inhibited after induction of the heat shock response in cultured rat pulmonary artery smooth mus cle cells (RPASMC). Exposure of RPASMC to sodium arsenite or heat led to expression of heat shock protein-70 (HSP-70) in a time- and concent ration-dependent manner. Prior induction of the heat shock response in hibited IL-1 beta-mediated iNOS gene expression in a time- and dose-de pendent manner. The inhibitory effects were not due to cytotoxicity, s ince cell viability was not affected by either sodium arsenite, heat, IL-1 beta, or their combination. Transcriptional analysis via transien t transfection of the murine macrophage iNOS promoter [-1592 and -367 base pairs (bp)], upstream from the reporter gene luciferase, revealed that the heat shock response did not affect IL-1 beta-mediated promot er activation, as measured by luciferase activity. We conclude that in duction of the heat shock response inhibits IL-1 beta-mediated iNOS ge ne expression in cultured RPASMC.