Posttranscriptional regulation of TNFalpha expression via eukaryotic initiation factor 4E (eIF4E) phosphorylation in mouse macrophages.

Research output: Contribution to journalArticle

Abstract

Resident mouse macrophages secrete Tumor necrosis factor α (TNFα) upon challenge with LPS. The production of TNFα is controlled not only at the transcription of the gene, but also by strong posttranscriptional regulation. When macrophages are stimulated with LPS different signal transduction pathways become activated. Here we show that the combination of the 2 kinases p38 and MEK and presumably ERK1/2 regulate translation of TNFα, through the downstream kinase Mnk1. TNFα production is inhibited in a concentration-dependent manner by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the inhibition targets posttranscriptional regulation and is paralleled by inhibition of the phosphorylation of eukaryotic initiation factor 4E (eIF4E). Unexpectedly, the activation/inhibition of MAPKAP kinase-2 (MK2) does not parallel TNFα production, arguing against a direct/immediate role for this kinase. On the basis of the present and previous results we propose that ARE-containing TNFα mRNA requires phosphorylation of eIF4E for initiation of translation.

Details

Authors
  • Karolina Andersson
  • Roger Sundler
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • CGP57380, Mnk, mRNA translation, SB203580, U0126
Original languageEnglish
Pages (from-to)52-57
JournalCytokine
Volume33
Issue number1
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes