Secretory phospholipase A2 elicits proinflammatory changes and upregulates the surface expression of Fas ligand in monocytic cells -: Potential relevance for atherogenesis
Secretory phospholipase A2 elicits proinflammatory changes and upregulates the surface expression of Fas ligand in monocytic cells -: Potential relevance for atherogenesis
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DOI：
10.1161/hh0102.102978
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发表时间：
2002-01-11
影响因子：
20.1
通讯作者：
Nieto, ML
中科院分区：
文献类型：
--
作者：
Hernández, M;Fuentes, L;Nieto, ML
IIA型分泌型磷脂酶A（2）（sPLA（2））是一种急性期反应物，在动脉粥样硬化形成中起作用，并在显示炎症特征的动脉粥样硬化动脉壁中表达。鉴于单核细胞在与动脉粥样硬化相关的炎症过程中的作用，这产生了一个相关的问题，涉及这种酶对单核细胞的生物学效应。在THP-1单核细胞中，sPLA（2）引起丝裂原活化蛋白激酶（MAPK）级联的p42丝裂原活化蛋白模块的轻度活化和c-Jun N-末端激酶的显著活化。这种激活显示出早期和晚期峰值，不同于肿瘤坏死因子-α（TNF-α）引起的激活，其仅显示第一个峰值。这伴随着花生四烯酸代谢的激活，从胞质磷脂酶A（2）（cPLA（2））的激活和环氧合酶-2（考克斯-2）表达的诱导来判断。sPLA（2）还诱导单核细胞趋化蛋白-1（MCP-1）的产生，并与TNF-α在考克斯-2诱导和MCP-1产生上显示出协同效应。sPLA（2）可上调单核细胞表面Fas配体的表达，但不影响单核细胞表面Fas的表达和细胞存活。总之，这些数据表明sPLA（2）的某些致动脉粥样硬化作用可以通过sPLA（2）结合结构与单核细胞的结合来发挥。最可能的是sPLA的M型受体（2），其产生MAPK级联的活化，诱导促炎表型，并上调Fas配体的细胞表面表达。
Type IIA secretory phospholipase A(2) (sPLA(2)) is an acute-phase reactant that plays a role in atherogenesis and is expressed in atherosclerotic arterial walls displaying inflammatory features. This generates a relevant question addressing the biological effects of this enzyme on monocytic cells, in view of the role of these cells in the inflammatory process associated with atherosclerosis. sPLA(2) produced a mild activation of the p42 mitogen-activated protein module of the mitogen-activated protein kinase (MAPK) cascade and a prominent activation of c-Jun N-terminal kinase in THP-1 monocytes. This activation showed both an early and a late peak, different from that elicited by tumor necrosis factor-alpha (TNF-alpha), which only showed the first peak. This was accompanied by activation of arachidonate metabolism, as judged from both the activation of the cytosolic phospholipase A(2) (cPLA(2)) and the induction of cyclooxygenase-2 (COX-2) expression. sPLA(2) also elicited the production of monocyte chemoattractant protein-1 (MCP-1) and showed a synergistic effect with TNF-alpha on both COX-2 induction and MCP-1 production. sPLA(2) upregulated the expression of Fas ligand at the cell surface, but it did not influence Fas expression nor cell survival of monocytes. In summary, these data indicate that some of the atherogenic effects of sPLA(2) can be exerted by engagement of an sPLA(2)-binding structure on monocytic cells. most probably the M-type receptor for sPLA(2), which produces the activation of the MAPK cascade, induces a proinflammatory phenotype, and upregulates the cell surface expression of Fas ligand.