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Regulation of tumour necrosis factor alpha mRNA stability by the mitogen-activated protein kinase p38 signalling

M Brook1, G Sully, A R Clark

  • 1Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, Hammersmith, W6 8LH, London, UK.

FEBS Letters
|October 18, 2000
PubMed

Insights

The stress-activated protein kinase p38 pathway regulates tumour necrosis factor alpha (TNFalpha) mRNA stability. Inhibition of p38 reversed TNFalpha mRNA stabilization, confirming its role in mRNA turnover.

Area of Science:

  • Molecular biology
  • Immunology
  • Cell signaling

Background:

  • Tumour necrosis factor alpha (TNFalpha) mRNA translation is regulated by stress-activated protein kinase p38.
  • p38 kinase also influences the stability of pro-inflammatory mRNAs.

Purpose of the Study:

  • To re-examine the regulation of TNFalpha gene expression in RAW264.7 cells.
  • To investigate the role of p38 in TNFalpha mRNA stability.

Main Methods:

  • Utilized a mouse macrophage cell line (RAW264.7).
  • Employed an inhibitor of stress-activated protein kinases.
  • Performed a tetracycline-regulated mRNA stability assay using an adenosine/uridine-rich element from TNFalpha 3' UTR.

Main Results:

  • Bacterial lipopolysaccharide stimulation stabilized TNFalpha mRNA in RAW264.7 cells.
  • Specific inhibition of p38 reversed this TNFalpha mRNA stabilization.
  • An adenosine/uridine-rich element conferred p38-sensitive decay in mRNA stability assays.

Conclusions:

  • The p38 pathway is a key regulator of TNFalpha mRNA turnover.
  • p38 kinase controls the stability of TNFalpha mRNA.
  • Findings elucidate a critical mechanism in inflammatory gene regulation.

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