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

Research output: Contribution to journalArticlepeer-review

Authors

  • Corina Tudor
  • Francesco P. Marchese
  • Edward Hitti
  • Anna Aubareda
  • Lesley Rawlinson
  • Matthias Gaestel
  • Perry J. Blackshear
  • Jeremy Saklatvala
  • Jonathan L.E. Dean

Colleges, School and Institutes

External organisations

  • Imperial College London
  • Institute of Biochemistry
  • National Institute of Environmental Health Sciences (NIEHS)
  • Kennedy Institute

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.

Details

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

Keywords

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