title: STAT-1 mediates the stimulatory effect of IL-10 on CD14 expression in human monocytic cells.
abstract: IL-10, an anti-inflammatory cytokine, has been shown to exhibit stimulatory functions including CD14 up-regulation on human monocytic cells. CD14-mediated signaling following LPS stimulation of monocytic cells results in the synthesis of proinflammatory cytokines. Our results show that LPS-induced CD14 expression on monocytic cells may be mediated by endogenously produced IL-10. To investigate the molecular mechanism by which IL-10 enhances CD14 expression, both human monocytes and the promyelocytic HL-60 cells were used as model systems. IL-10 induced the phosphorylation of PI3K and p42/44 ERK MAPK. By using specific inhibitors for PI3K (LY294002) and ERK MAPKs (PD98059), we demonstrate that LY294002 either alone or in conjunction with PD98059 inhibited IL-10-induced phosphorylation of STAT-1 and consequently CD14 expression. However, IL-10-induced STAT-3 phosphorylation remained unaffected under these conditions. Finally, STAT-1 interfering RNA inhibited IL-10-induced CD14 expression. Taken together, these results suggest that IL-10-induced CD14 up-regulation in human monocytic cells may be mediated by STAT-1 activation through the activation of PI3K either alone or in concert with the ERK MAPK.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ali Akbar Rahim
authors.initials: AA
authors.lastname: Rahimi
authors.forename: Katrina
authors.initials: K
authors.lastname: Gee
authors.forename: Sasmita
authors.initials: S
authors.lastname: Mishra
authors.forename: Wilfred
authors.initials: W
authors.lastname: Lim
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009000:Monocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D020298:U937 Cells; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases