Induction of the stress response with prostaglandin A 1 increases I‐κBα gene expression

I‐κBα is an intracellular protein that functions as a primary inhibitor of the proinflammatory transcription factor NF‐κB. Induction of the stress response with heat shock was previously demonstrated to induce I‐κBα 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‐κBα 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‐κBα mRNA expression in a time‐dependent manner and increased I‐κBα peptide expression. Transient transfection assays involving a human I‐κBα promoter‐luciferase reporter construct demonstrated that induction of the stress response with PGA 1 activated the I‐κBα promoter. Induction of the stress response with PGA 1 and concomitant induction of I‐κBα were associated with inhibition of TNF‐α‐mediated secretion of interleukin 8 and with inhibition of TNF‐α‐mediated nuclear translocation and activation of NF‐κB. These data demonstrate that induction of the stress response, by a nonthermal stimulus, increases I‐κBα gene expression by a mechanism involving activation of the I‐κBα promoter. Coupled with previous data demonstrating heat shock‐mediated induction of I‐κBα gene expression, these data suggest that I‐κBα may be considered to be one of the stress proteins. The functional consequences of stress response‐mediated I‐κBα 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‐ĸBα gene expression. FASEB J. 12, 1371–1378 (1998)