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(Journal of Leukocyte Biology. 2002;71:1026-1032.)
© 2002 by Society for Leukocyte Biology

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

Dept. de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain

Correspondence: Dr. Simon MacKenzie, Dept. Cell Biology, Physiology & Immunology, Unit of Animal Physiology, Edifici C, Universitat Autonoma de Barcelona, 08193-Bellaterra, Spain. E-mail: Simon.MacKenzie{at}uab.es

Tumor necrosis factor (TNF-), a proinflammatory cytokine, is produced abundantly by monocytes and macrophages. We have compared LPS-stimulated TNF- production and regulation in freshly isolated human monocytes and macrophages differentiated in vitro. A significant increase in LPS-induced TNF- protein secretion was observed in macrophages over freshly isolated monocytes without comparable differences in TNF- mRNA induction. Polysome gradient analysis showed polysome-mRNA distribution did not change, whereas TNF- 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- biosynthesis differentially at the transcriptional and post-transcriptional level throughout the culture period. We suggest that the increase in TNF- 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.

Key Words: translation • stability • MAPK • tristetraprolin

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