Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Korea.
Exp Mol Med. 2010 Apr 30;42(4):302-9. doi: 10.3858/emm.2010.42.4.029.
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.
血清淀粉样蛋白 A(SAA)通过百日咳毒素(PTX)不敏感途径诱导人脐静脉内皮细胞(HUVEC)中 CCL2 的产生。SAA 诱导三种 MAPK(ERK、p38 MAPK 和 JNK)的激活,该激活可被甲酰肽受体 2(FPR2)敲低完全抑制。通过其特异性抑制剂(SB203580 和 SP600125)抑制 p38 MAPK 和 JNK,或通过 p38 MAPK 的显性负突变体抑制,均可显著降低 SAA 诱导的 CCL2 产生。PTX 使 G(i)蛋白失活可抑制 SAA 诱导的 ERK 的激活,但不抑制 p38 MAPK 或 JNK 的激活。结果表明,SAA 刺激 FPR2 介导的 p38 MAPK 和 JNK 的激活,该激活不依赖于 PTX 敏感的 G 蛋白,是 SAA 诱导 CCL2 产生所必需的。