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Inflammation Research

, Volume 55, Issue 6, pp 254–259 | Cite as

Mechanism and function of heat shock-dependent IκBα expression

  • K. E. Dunsmore
  • A. G. Denenberg
  • K. Page
  • H. R. Wong
Original Research Paper

Abstract.

Objective

Heat shock is known to inhibit activation of the NF-κ B pathway. One potential mechanism of this effect is de novo expression of the intracellular NF-κB inhibitor, Iκ Bα. Herein we sought to elucidate the mechanisms by which heat shock induces Iκ Bα gene expression and the functional consequences of heat shock-mediated Iκ Bα gene expression in A549 cells.

Methods

Nuclear run-on assays demonstrated that heat shock had a small effect on transcription of the Iκ Bα gene relative to the level of steady state Iκ Bα mRNA that is seen following heat shock. Accordingly, we determined the effect of heat shock on Iκ Bα mRNA stability by treating cells with actinomycin D to induce transcriptional arrest.

Results

The half-life of IκBα mRNA was 36  ±  7.2 min in control cells and 101  ±  3.7 min in cells subjected to heat shock. These data were consistent with heat shock-mediated increased stability of Iκ Bα mRNA. Heat shock induced activation of p38 MAP kinase and inhibition of p38 MAP kinase substantially reduced heat shock-dependent expression of Iκ Bα mRNA. After a 4 h recovery period from heat shock, there was inhibition of tumor necrosis factor-α-mediated NF-κB activation. The introduction of an Iκ Bα anti-sense oligonucleotide reversed this inhibitory effect of heat shock.

Conclusions

We conclude that heat shock increases IκBα gene expression primarily by increasing Iκ Bα mRNA stability and this effect is partially dependent on p38 MAP kinase. The functional consequence of heat shock-mediated Iκ Bα gene expression is inhibition of NF-κB activation.

Key words.

Heat shock I B mRNA stability p38 

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Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  • K. E. Dunsmore
    • 1
    • 2
  • A. G. Denenberg
    • 1
    • 2
  • K. Page
    • 1
    • 2
  • H. R. Wong
    • 1
    • 2
  1. 1.Division of Critical Care MedicineCincinnati Children’s Hospital Medical Center and Cincinnati Children’s Research FoundationCincinnatiUSA
  2. 2.Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiUSA

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