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

作者：MacKenzie S^*; Fernandez Troy N; Espel E

来源：Journal of Leukocyte Biology, 2002, 71(6): 1026-1032.

DOI：10.1189/jlb.71.6.1026

• translation
• stability
• MAPK
• tristetraprolin

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

• 出版日期2002-6