The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages

Corina Tudor, Francesco P. Marchese, Edward Hitti, Anna Aubareda, Lesley Rawlinson, Matthias Gaestel, Perry J. Blackshear, Andrew R. Clark, Jeremy Saklatvala, Jonathan L.E. Dean*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

p38 mitogen-activated protein kinase (MAPK) stabilises pro-inflammatory mediator mRNAs by inhibiting AU-rich element (ARE)-mediated decay. We show that in bone-marrow derived murine macrophages tristetraprolin (TTP) is necessary for the p38 MAPK-sensitive decay of several pro-inflammatory mRNAs, including cyclooxygenase-2 and the novel targets interleukin (IL)-6, and IL-1α. TTP-/- macrophages also strongly overexpress IL-10, an anti-inflammatory cytokine that constrains the production of the IL-6 despite its disregulation at the post-transcriptional level. TTP directly controls IL-10 mRNA stability, which is increased and insensitive to inhibition of p38 MAPK in TTP-/- macrophages. Furthermore, TTP enhances deadenylation of an IL-10 3′-untranslated region RNA in vitro.

Original languageEnglish
Pages (from-to)1933-1938
Number of pages6
JournalFEBS Letters
Volume583
Issue number12
DOIs
Publication statusPublished - 18 Jun 2009

Keywords

  • COX-2
  • Interleukin-10
  • p38 Mitogen-activated protein kinase
  • Tristetraprolin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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