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

Samuel C. Thomas, Marnie A. Ryan, Thomas P. Shanley, Hector R. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)1371-1378
Number of pages8
JournalFASEB Journal
Volume12
Issue number13
StatePublished - Oct 28 1998

Keywords

  • Inflammation
  • Interleukin 8
  • NF-κB
  • PGA

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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