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.
Highlights
Serum amyloid A (SAA), a major acute-phase protein, is an important component of responses to infection or injury (Uhlar and Whitehead, 1999)
Since SAA has been reported to act on formyl peptide receptor 2 (FPR2), we tested the effect of WRW4, an FPR2 antagonist, on SAA-induced CCL2 production in human umbilical vein endothelial cells (HUVECs)
Pre-incubation of HUVECs with WRW4 prior to SAA addition caused dramatic inhibition of CCL2 production induced by SAA (Figure 1C), indicating that SAA acts on FPR2, resulting in CCL2 production in HUVECs
Summary
Serum amyloid A (SAA), a major acute-phase protein, is an important component of responses to infection or injury (Uhlar and Whitehead, 1999). It has been shown that SAA has cytokine-like properties by modulating several cellular responses (Badolato et al, 1994; Jijon et al, 2005; Lee et al, 2006a; Koga et al, 2008). SAA stimulates production of several cytokines from different cell types, including monocytes, epithelial cells, and synovial cells (Jijon et al, 2005; Lee et al, 2006a; Koga et al, 2008). We have recently reported that SAA stimulates CCL2 production by human umbilical vein endothelial cells (HUVECs; Lee et al, 2009)
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