title: A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production.
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.
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Sang Doo
authors.initials: SD
authors.lastname: Kim
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Shim
authors.forename: Hak Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jeanho
authors.initials: J
authors.lastname: Yun
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D018932:Chemokine CCL2 / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D000685:Serum Amyloid A Protein; D037342:Pertussis Toxin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins