Serum amyloid A induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes.

Abstract

Although the presence of an elevated level of serum amyloid A (SAA) has been regarded as a cardiovascular risk factor, the role of SAA on the progress of atherosclerosis has not been fully elucidated. In the present study, we investigated the effect of SAA on the production of CCL2, an important mediator of monocyte recruitment, and the mechanism underlying the action of SAA in human monocytes. The stimulation of human monocytes with SAA elicited CCL2 production in a concentration-dependent manner. The production of CCL2 by SAA was found to be mediated by the activation of NF-kappaB. Moreover, the signaling events induced by SAA included the activation of ERK and the induction of cyclooxygenase-2, which were required for the production of CCL2. Moreover, SAA-induced CCL2 induction was inhibited by a formyl peptide receptor-like 1 (FPRL1) antagonist. We also found that the stimulation of FPRL1-expressing RBL-2H3 cells induced CCL2 mRNA accumulation, but the vector-expressing RBL-2H3 cells combined with SAA did not. Taken together, our findings suggest that SAA stimulates CCL2 production and, thus, contributes to atherosclerosis. Moreover, FPRL1 was found to be engaged in SAA-induced CCL2 induction, and cyclooxygenase-2 induction was found to be essential for SAA-induced CCL2 expression. These results suggest that SAA and FPRL1 offer a developmental starting point for the treatment of atherosclerosis.

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@article{Lee2008SerumAA, title={Serum amyloid A induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes.}, author={Ha Young Lee and Sang Doo Kim and Jae Woong Shim and Sun Young Lee and Hwahyung Lee and Kyung-Hyun Cho and Jeanho Yun and Yoe-Sik Bae}, journal={Journal of immunology}, year={2008}, volume={181 6}, pages={4332-9} }