Post-transcriptional regulation of TNF-α during in vitro differentiation of human monocytes/macrophages in primary culture

Citation

MacKenzie S, Fernandez-Troy N & Espel E (2002) Post-transcriptional regulation of TNF-α during in vitro differentiation of human monocytes/macrophages in primary culture. Journal of Leukocyte Biology, 71 (6), pp. 1026-1032. http://www.jleukbio.org/content/71/6/1026.short

Abstract
Tumor necrosis factor α (TNF-α), a proinflammatory cytokine, is produced abundantly by monocytes and macrophages. We have compared LPS-stimulated TNF-α production and regulation in freshly isolated human monocytes and macrophages differentiated in vitro. A significant increase in LPS-induced TNF-α protein secretion was observed in macrophages over freshly isolated monocytes without comparable differences in TNF-α mRNA induction. Polysome gradient analysis showed polysome-mRNA distribution did not change, whereas TNF-α mRNA stability increased in macrophages. Tristetraprolin mRNA expression was constitutive and decreased with differentiation-linked kinetics. Blockable LPS-inducible MAP kinase activity (p38, ERK) affected TNF-α biosynthesis differentially at the transcriptional and post-transcriptional level throughout the culture period. We suggest that the increase in TNF-α secretion in macrophages relates to changes in post-transcriptional processing, which is regulated indirectly by the expression of RNA-binding proteins. Changes in gene expression throughout monocytic differentiation equip the cell to act as a more potent producer of this proinflammatory cytokine.

Keywords
translation; stability; MAPK; tristetraprolin

Journal
Journal of Leukocyte Biology: Volume 71, Issue 6