Induction of the stress response with prostaglandin A1 increases I-κBα gene expression

I-kappa B alpha is an intracellular protein that functions as a primary inhibitor of the proinflammatory transcription factor NF-KB. 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 A(1) (PGA(1)) would induce I-kappa B alpha gene expression. Treatment of human bronchial epithelium (BEAS-2B cells) with PGA(1) induced nuclear translocation of heat shock factor 1, thus confirming that PGA(1) induces the stress response in BEAS-2B cells. Induction of the stress response with PGA(1) 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.