Phosphatidylserine inhibits NFκB and p38 MAPK activation in human monocyte derived dendritic cells.
Phosphatidylserine inhibits NFκB and p38 MAPK activation in human monocyte derived dendritic cells.
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DOI：
10.1016/j.molimm.2011.04.021
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发表时间：
2011-09
影响因子：
3.6
通讯作者：
K. Doffek;Xiao Chen;S. Sugg;J. Shilyansky
中科院分区：
文献类型：
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作者：
K. Doffek;Xiao Chen;S. Sugg;J. Shilyansky
磷脂酰丝氨酸(PS)是一种限制在质膜内表面的阴离子磷脂。PS在早期细胞凋亡时被转移到细胞表面，在那里它作为吞噬细胞快速摄取的标志。PS还被认为可以调节免疫反应。树突状细胞(DC)是功能最强的抗原提呈细胞。先前的研究表明，PS抑制人单核细胞来源的DC表达MHC和共刺激分子，分泌IL-12p70，以及激活T细胞的能力。然而，PS调控DC的细胞信号机制还没有得到很好的描述。在目前的研究中，我们测试了PS对被认为调节人髓系DC成熟和IL-12p70产生的信号转导通路的影响。我们发现PS通过阻止IκBκ的磷酸化和降解来抑制核因子κB(NFαB)的激活。PS还可增加未成熟DC的总IκBα水平，抑制p38丝裂原活化蛋白激酶的磷酸化和活化。这些发现提示了PS调节DC免疫刺激功能的可能机制。
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.