STAT-1 Mediates the Stimulatory Effect of IL-10 on CD14 Expression in Human Monocytic Cells

• Published in: The Journal of immunology (1950) 2005-06, Vol.174 (12), p.7823-7832
• Main Authors: Rahimi, Ali Akbar Rahim, Gee, Katrina, Mishra, Sasmita, Lim, Wilfred, Kumar, Ashok
• Format: Article
• Language: English
• Subjects: Adult; Cell Line, Tumor; Cell Membrane - immunology; Cell Membrane - metabolism; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Drug Synergism; Extracellular Signal-Regulated MAP Kinases - physiology; HL-60 Cells; Humans; Interleukin-10 - physiology; Lipopolysaccharide Receptors - biosynthesis; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Mitogen-Activated Protein Kinases - physiology; Monocytes - enzymology; Monocytes - immunology; Monocytes - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol 3-Kinases - physiology; Signal Transduction - immunology; STAT1 Transcription Factor; STAT3 Transcription Factor; Trans-Activators - metabolism; Trans-Activators - physiology; U937 Cells; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7823

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.