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 language | English |
---|---|
Pages (from-to) | 1933-1938 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 583 |
Issue number | 12 |
DOIs | |
Publication status | Published - 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