Exp Mol Med.  2010 Apr;42(4):302-309. 10.3858/emm.2010.42.4.029.

A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production

Affiliations
  • 1Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Korea. yoesik@skku.edu
  • 2Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Korea.
  • 3Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Korea.
  • 4Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
  • 5Department of Pharmacology, Pusan National University College of Medicine, Yangsan 628-870, Korea.

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 Gi 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.

Keyword

atherosclerosis; chemokine CCL2; endothelial cells; FPR2 protein, human; pertussis toxin; serum amyloid A protein
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