title: Phosphatidylserine inhibits NFκB and p38 MAPK activation in human monocyte derived dendritic cells.
abstract: Phosphatidylserine (PS) is an anionic phospholipid restricted to the inner surface of the plasma membrane. PS translocates to the cell surface during early apoptosis where it serves as a marker for rapid uptake by phagocytes. PS is also thought to regulate immune responses. Dendritic cells (DC) are the most potent antigen presenting cells. Previous studies demonstrated that PS inhibits the expression of MHC and co-stimulatory molecules, the secretion of IL-12p70, and the ability to activate T cells by human monocyte derived DCs. However, the cell signaling mechanisms by which PS regulated DCs are not well described. In the current study we tested the effects of PS on signal transduction pathways thought to regulate human myeloid DC maturation and IL-12p70 production. We showed that PS inhibited the activation of nuclear factor-κB (NFκB) in response to LPS by preventing IκBα phosphorylation and degradation. PS also increased the total IκBα levels in immature DCs and inhibited p38 mitogen activated protein kinase (MAPK) phosphorylation and activation. The findings suggest a possible mechanism for regulating the immunostimulatory function of DCs by PS.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: Kara
authors.initials: K
authors.lastname: Doffek
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Sugg
authors.forename: Joel
authors.initials: J
authors.lastname: Shilyansky
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D010718:Phosphatidylserines; D048051:p38 Mitogen-Activated Protein Kinases