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 A1 (PGA1) would induce I-κBα 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-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 PGA1 activated the I-κBα promoter. Induction of the stress response with PGA1 and concomitant induction of I-κBα were associated with inhibition of TNF-α-mediated secretion of interleukin 8 and with inhibition of WNF-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.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Oct 28 1998|
- Interleukin 8
ASJC Scopus subject areas
- Molecular Biology