Interleukin-10-induced CCR5 expression in macrophage like HL-60 cells: involvement of Erk1/2 and STAT-3.
As an immunosuppressive and anti-inflammatory cytokine, IL-10 was recently reported to play roles in CCR5 expression in human monocytes. CCR5 promoter regions contain Oct-2, TCF-1alpha, GATA, and STAT binding sites. Here, we studied the signals involved in the CCR5 expression in IL-10-stimulated cells using the HL-60 cell line. HL-60 cells were stimulated with PMA and differentiated to macrophage-like cells, then stimulated with IL-10. IL-10 induced significant expression of CCR5 protein and CCR5 mRNA in these cells. The induction of CCR5 by IL-10 was inhibited by a MEK-1 inhibitor, PD98059. In addition, IL-10 induced tyrosine (Tyr) phosphorylation of Erk, as well as serine (Ser) and Tyr phosphorylation of STAT-3. Tyr phosphorylation of Erk and Ser phosphorylation of STAT-3 were inhibited by PD98059, while Tyr phosphorylation of STAT-3 was not inhibited by PD98059. DNA binding activity of STAT-3 was observed by the stimulation with IL-10, which was inhibited by PD98059. These results first indicate that Erk1/2 and STAT-3 regulate CCR5 expression, and that Erk-mediated phosphorylation of Ser is required for full stimulation of STAT-3 in CCR5 expression.
Makuta
Yoko
Y
Department of Biochemistry, Kyoritsu College of Pharmacy, Tokyo, Japan.
Sonoda
Yoshiko
Y
Yamamoto
Daisuke
D
Funakoshi-Tago
Megumi
M
Aizu-Yokota
Eriko
E
Takebe
Yutaka
Y
Kasahara
Tadashi
T
D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology*
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D012333:RNA, Messenger; D019713:Receptors, CCR5; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016753:Interleukin-10; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one