Serum amyloid a induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes
Serum amyloid a induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes
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DOI：
10.4049/jimmunol.181.6.4332
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发表时间：
2008-09-15
影响因子：
4.4
通讯作者：
Bae, Yoe-Sik
中科院分区：
文献类型：
--
作者：
Lee, Ha Young;Kim, Sang Doo;Bae, Yoe-Sik
尽管血清淀粉样蛋白 A (SAA) 水平升高已被视为心血管危险因素，但 SAA 在动脉粥样硬化进展中的作用尚未完全阐明。在本研究中，我们研究了 SAA 对 CCL2（单核细胞募集的重要介质）产生的影响，以及 SAA 在人类单核细胞中作用的机制。用 SAA 刺激人单核细胞会以浓度依赖性方式引发 CCL2 的产生。研究发现，SAA 产生的 CCL2 是由 NF-κ B 的激活介导的。此外，SAA 诱导的信号转导事件包括 ERK 的激活和环氧合酶-2 的诱导，这是产生 CCL2 所必需的。此外，SAA 诱导的 CCL2 诱导被甲酰肽受体样 1 (FPRL1) 拮抗剂抑制。我们还发现，刺激表达 FPRL1 的 RBL-2H3 细胞会诱导 CCL2 mRNA 积累，但表达载体的 RBL-2H3 细胞与 SAA 结合则不会。综上所述，我们的研究结果表明 SAA 刺激 CCL2 的产生，从而导致动脉粥样硬化。此外，发现 FPRL1 参与 SAA 诱导的 CCL2 诱导，并且发现环氧合酶 2 诱导对于 SAA 诱导的 CCL2 表达至关重要。这些结果表明 SAA 和 FPRL1 为动脉粥样硬化的治疗提供了一个发展起点。
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-kappa B. 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.