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The p38 MAPK pathway inhibits tristetraprolin‐directed decay of interleukin‐10 and pro‐inflammatory mediator mRNAs in murine macrophages
Author(s) -
Tudor Corina,
Marchese Francesco P.,
Hitti Edward,
Aubareda Anna,
Rawlinson Lesley,
Gaestel Matthias,
Blackshear Perry J.,
Clark Andrew R.,
Saklatvala Jeremy,
Dean Jonathan L.E.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.04.039
Subject(s) - tristetraprolin , p38 mitogen activated protein kinases , mediator , microbiology and biotechnology , mapk/erk pathway , cytokine , au rich element , messenger rna , chemistry , inflammation , kinase , proinflammatory cytokine , macrophage , untranslated region , in vitro , biology , immunology , biochemistry , gene
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.