Abstract
Serum amyloid A (SAA) induced CCL2 production via a pertussis toxin (PTX)-insensitive pathway in human umbilical vein endothelial cells (HUVECs). SAA induced the activation of three MAPKs (ERK, p38 MAPK, and JNK), which were completely inhibited by knock-down of formyl peptide receptor 2 (FPR2). Inhibition of p38 MAPK and JNK by their specific inhibitors (SB203580 and SP600125), or inhibition by a dominant negative mutant of p38 MAPK dramatically decreased SAA-induced CCL2 production. Inactivation of G((i)) protein(s) by PTX inhibited the activation of SAA-induced ERK, but not p38 MAPK or JNK. The results indicate that SAA stimulates FPR2-mediated activation of p38 MAPK and JNK, which are independent of a PTX-sensitive G-protein and are essential for SAA-induced CCL2 production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chemokine CCL2 / biosynthesis*
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Endothelial Cells / enzymology
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GTP-Binding Proteins / metabolism*
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Pertussis Toxin / pharmacology*
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Receptors, Formyl Peptide / metabolism*
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Receptors, Lipoxin / metabolism*
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Serum Amyloid A Protein / pharmacology*
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Signal Transduction / drug effects*
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Umbilical Veins / cytology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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CCL2 protein, human
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Chemokine CCL2
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FPR2 protein, human
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Receptors, Formyl Peptide
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Receptors, Lipoxin
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Serum Amyloid A Protein
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Pertussis Toxin
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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GTP-Binding Proteins