Regulation of tumour necrosis factor α mRNA stability by the mitogen‐activated protein kinase p38 signalling cascade

Abstract
The translation of tumour necrosis factor α (TNFα) mRNA is regulated by the stress‐activated protein kinase p38, which also controls the stability of several pro‐inflammatory mRNAs. The regulation of TNFα gene expression in a mouse macrophage cell line RAW264.7 was re‐examined using an inhibitor of stress‐activated protein kinases. Stimulation of these cells with bacterial lipopolysaccharide resulted in stabilisation of TNFα mRNA, which was reversed by specific inhibition of p38. An adenosine/uridine‐rich element from the TNFα 3′ untranslated region conferred p38‐sensitive decay in a tetracycline‐regulated mRNA stability assay. Therefore the p38 pathway also controls TNFα mRNA turnover.