title: Secretory phospholipase A(2) elicits proinflammatory changes and upregulates the surface expression of fas ligand in monocytic cells: potential relevance for atherogenesis.
abstract: 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.
authors.affiliation: Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Valladolid, Spain.
authors.forename: Marita
authors.initials: M
authors.lastname: Hernández
authors.forename: Lucía
authors.initials: L
authors.lastname: Fuentes
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Fernández Avilés
authors.forename: Mariano Sánchez
authors.initials: MS
authors.lastname: Crespo
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Nieto
mesh_terms: D001161:Arteriosclerosis / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein; D005419:Flavonoids / Q000494:pharmacology; D054501:Group II Phospholipases A2; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D054507:Receptors, Phospholipase A2; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005419:Flavonoids; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016328:NF-kappa B; C516360:PLA2R1 protein, human; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one