PMID- 11786516
OWN - NLM
STAT- MEDLINE
DCOM- 20020423
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 90
IP  - 1
DP  - 2002 Jan 11
TI  - Secretory phospholipase A(2) elicits proinflammatory changes and upregulates the 
      surface expression of fas ligand in monocytic cells: potential relevance for 
      atherogenesis.
PG  - 38-45
AB  - 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.
FAU - Hernandez, Marita
AU  - Hernandez M
AD  - Instituto de Biologia y Genetica Molecular, Consejo Superior de Investigaciones 
      Cientificas, Facultad de Medicina, Valladolid, Spain.
FAU - Fuentes, Lucia
AU  - Fuentes L
FAU - Fernandez Aviles, Francisco Javier
AU  - Fernandez Aviles FJ
FAU - Crespo, Mariano Sanchez
AU  - Crespo MS
FAU - Nieto, Maria Luisa
AU  - Nieto ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Chemokine CCL2)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Flavonoids)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (PLA2R1 protein, human)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Phospholipase A2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Group II Phospholipases A2)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Arteriosclerosis/enzymology/metabolism
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Cyclooxygenase 2
MH  - Enzyme Activation/drug effects
MH  - Fas Ligand Protein
MH  - Flavonoids/pharmacology
MH  - Group II Phospholipases A2
MH  - Humans
MH  - Isoenzymes/metabolism
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - Membrane Glycoproteins/*metabolism
MH  - Membrane Proteins
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/cytology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Phospholipases A/*metabolism/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Phospholipase A2
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation
EDAT- 2002/01/12 10:00
MHDA- 2002/04/24 10:01
CRDT- 2002/01/12 10:00
PHST- 2002/01/12 10:00 [pubmed]
PHST- 2002/04/24 10:01 [medline]
PHST- 2002/01/12 10:00 [entrez]
AID - 10.1161/hh0102.102978 [doi]
PST - ppublish
SO  - Circ Res. 2002 Jan 11;90(1):38-45. doi: 10.1161/hh0102.102978.