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RESEARCH COMMUNICATION |
B
gene expression
a Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
I-
B
is an intracellular protein that functions as a primary inhibitor of the proinflammatory transcription factor NF-
B. Induction of the stress response with heat shock was previously demonstrated to induce I-
B
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-
B
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-
B
mRNA expression in a time-dependent manner and increased I-
B
peptide expression. Transient transfection assays involving a human I-
B
promoter-luciferase reporter construct demonstrated that induction of the stress response with PGA1 activated the I-
B
promoter. Induction of the stress response with PGA1 and concomitant induction of I-
B
were associated with inhibition of TNF-
-mediated secretion of interleukin 8 and with inhibition of TNF-
-mediated nuclear translocation and activation of NF-
B. These data demonstrate that induction of the stress response, by a nonthermal stimulus, increases I-
B
gene expression by a mechanism involving activation of the I-
B
promoter. Coupled with previous data demonstrating heat shock-mediated induction of I-
B
gene expression, these data suggest that I-
B
may be considered to be one of the stress proteins. The functional consequences of stress response-mediated I-
B
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-
B
gene expression. FASEB J. 12, 13711378 (1998)
Key Words: PGA1 NF-
B interleukin 8 inflammation
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