title: Differential regulation of eotaxin expression by TNF-alpha and PMA in human monocytic U-937 cells.
abstract: Regulation of eotaxin expression was investigated in U-937 cells, a human monocyte-like cell line. Eotaxin mRNA was induced by tumor necrosis factor-alpha (TNF-alpha; 0.1-100 ng/ml) and phorbol 12-myristate 13-acetate (PMA; 0.01-1 microM). PMA-induced eotaxin mRNA expression was of greater magnitude and was maximal at a later time point than TNF-alpha-induced expression (16 h vs. 2 h after stimulation), which was consistent with eotaxin protein expression detected by immunocytochemistry. Dexamethasone (0.01-10 microM) decreased eotaxin mRNA expression in both TNF-alpha- and PMA-stimulated U-937 cells. PMA-induced eotaxin mRNA expression was inhibited by cycloheximide (10 microg/ml), whereas TNF-alpha-induced expression was not. The protein kinase C (PKC) inhibitor staurosporine (10-50 nM) inhibited PMA-induced eotaxin mRNA expression, whereas TNF-alpha-induced expression was enhanced by this reagent. These results suggest that eotaxin expression can be induced by more than one mechanism: the PMA-triggered pathway is mediated by PKC activation and requires new protein synthesis, whereas the TNF-alpha-triggered pathway is independent of PKC and protein synthesis. TNF-alpha- and PMA-induced pathways are both associated with nuclear factor-kappaB, because its binding activity was enhanced in the presence of these stimuli, and both pathways were limited by its inhibitor, diethyldithiocarbamate.
authors.affiliation: Combined Program in Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: K J
authors.initials: KJ
authors.lastname: Haley
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: A D
authors.initials: AD
authors.lastname: Luster
authors.forename: C M
authors.initials: CM
authors.lastname: Lilly
mesh_terms: D000230:Adenocarcinoma; D002460:Cell Line; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate