HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, H. Y. Articles by Bae, Y.-S. Search for Related Content PubMed PubMed Citation Articles by Lee, H. Y. Articles by Bae, Y.-S.

Serum Amyloid A Induces CCL2 Production via Formyl Peptide Receptor-Like 1-Mediated Signaling in Human Monocytes¹

Ha Young Lee^*, Sang Doo Kim^*, Jae Woong Shim^*, Sun Young Lee^*, Hwahyung Lee, Kyung-Hyun Cho, Jeanho Yun^* and Yoe-Sik Bae^2,*

^* Department of Biochemistry, College of Medicine, Dong-A University, Busan, Korea; and School of Biotechnology, Yeungnam University, Gyeongsan, Korea

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-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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Korea Science and Engineering Foundation Grant R01-2007-000-11241-0 funded by the Korean government (Ministry of Science and Technology) and by Korea Health 21 Research and Development Project Grant A060065 from the Ministry of Health and Welfare, Republic of Korea.

² Address correspondence and reprint request to Dr. Yoe-Sik Bae, Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Korea. E-mail address: yoesik{at}donga.ac.kr

³ Abbreviations used in this paper: SAA, serum amyloid A; ActD, actinomycin D; apoA-I, apolipoprotein A-I; BAY 11-7082, (E)-3-[4(4-methylphenyl)-sulfonyl]-2-propenenitrile; CHX, cycloheximide; COX-2, cyclooxygenase-2; FPR, formyl peptide receptor; FPRL1, FPR-like 1; HDL, high density lipoprotein; NS398, N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; PD98059, 2'-amino-3'-methoxyflavone; PTX, pertussis toxin; POPC, 1-palmitoyl-2-oleoylphosphatidylcholine; SB203580, 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole.

Related articles in The JI:

IN THIS ISSUE

The JI 2008 181: 3729-3730. [Full Text]