Se-methylselenocysteine enhances PMA-mediated CD11c expression via phospholipase D1 activation in U937 cells.
CD11c/CD18 is expressed primarily on myeloid cells, where its expression is regulated both during differentiation and during monocyte maturation into tissue macrophages, and is also a receptor for fibrinogen and lipopolysaccharide (LPS). We focused on the molecular mechanisms leading to the activation of CD11c expression in differentiating U937 cells. During phorbol myristate acetate (PMA)-induced differentiation of U937 cells, we found that the mRNA expression of CD11c was increased. Se-methylselenocysteine (Se-MSC) potentiated up-regulation of CD11c expression and its promoter activity and increased PLD1 activity without affecting the level of PLD1 protein in PMA-treated cells. To examine the regulation mechanism of PMA and Se-MSC on CD11c gene expression through the activation of PLD1, we analyzed changes in the CD11c mRNA level and the promoter activity following treatment of a selective PLD inhibitor n-butanol. The combinatory effect of PMA and Se-MSC on CD11c gene expression was abolished by n-butanol in a dose-dependent manner. Further, introduction of PLD1 gene into U937 cells increased CD11c mRNA expression and activated CD11c promoter activity in a dose-dependent manner. These results showed that Se-MSC increased PMA-induced CD11c expression through the activation of PLD1 signaling pathway. To our knowledge, this is the first report that expression of the CD11c gene is regulated by PLD1 and is enhanced by Se-MSC during PMA-induced U937 differentiation.
Lee
Tae-Jin
TJ
Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, Republic of Korea. taejin@kmu.ac.kr
Kim
Young Ho
YH
Min
Do Sik
do S
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
D039521:CD11c Antigen / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017279:Selenocysteine / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D020298:U937 Cells; D015854:Up-Regulation
D039521:CD11c Antigen; D004791:Enzyme Inhibitors; D016566:Organoselenium Compounds; D017279:Selenocysteine; D010739:Phospholipase D; C106801:phospholipase D1; D003545:Cysteine; D013755:Tetradecanoylphorbol Acetate; C002979:selenomethylselenocysteine