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(The FASEB Journal. 1998;12:1371-1378.)
© 1998 FASEB


RESEARCH COMMUNICATION

Induction of the stress response with prostaglandin A1 increases I-{kappa}B{alpha} gene expression

Samuel C. Thomasa, Marnie A. Ryana, Thomas P. Shanleya, and Hector R. Wonga,1

a Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA

I-{kappa}B{alpha} is an intracellular protein that functions as a primary inhibitor of the proinflammatory transcription factor NF-{kappa}B. Induction of the stress response with heat shock was previously demonstrated to induce I-{kappa}B{alpha} gene expression. Because the stress response can also be induced by nonthermal stimuli, we determined whether induction of the stress response with prostaglandin A1 (PGA1) would induce I-{kappa}B{alpha} gene expression. Treatment of human bronchial epithelium (BEAS-2B cells) with PGA1 induced nuclear translocation of heat shock factor 1, thus confirming that PGA1 induces the stress response in BEAS-2B cells. Induction of the stress response with PGA1 increased I-{kappa}B{alpha} mRNA expression in a time-dependent manner and increased I-{kappa}B{alpha} peptide expression. Transient transfection assays involving a human I-{kappa}B{alpha} promoter-luciferase reporter construct demonstrated that induction of the stress response with PGA1 activated the I-{kappa}B{alpha} promoter. Induction of the stress response with PGA1 and concomitant induction of I-{kappa}B{alpha} were associated with inhibition of TNF-{alpha}-mediated secretion of interleukin 8 and with inhibition of TNF-{alpha}-mediated nuclear translocation and activation of NF-{kappa}B. These data demonstrate that induction of the stress response, by a nonthermal stimulus, increases I-{kappa}B{alpha} gene expression by a mechanism involving activation of the I-{kappa}B{alpha} promoter. Coupled with previous data demonstrating heat shock-mediated induction of I-{kappa}B{alpha} gene expression, these data suggest that I-{kappa}B{alpha} may be considered to be one of the stress proteins. The functional consequences of stress response-mediated I-{kappa}B{alpha} gene expression may involve attenuation of cellular proinflammatory responses.—Thomas, S. C., Ryan, M. A., Shanley, T. P., Wong, H. R. Induction of the stress response with prostaglandin A1 increases I-{kappa}B{alpha} gene expression. FASEB J. 12, 1371–1378 (1998)


Key Words: PGA1 • NF-{kappa}B • interleukin 8 • inflammation




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