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The Journal of Immunology, 2008, 181, 22 -26
Copyright © 2008 by The American Association of Immunologists, Inc.

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Cutting Edge: TLR2 Is a Functional Receptor for Acute-Phase Serum Amyloid A1

Ni Cheng, Rong He, Jun Tian, Patrick P. Ye and Richard D. Ye2

Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612

Induced secretion of acute-phase serum amyloid A (SAA) is a host response to danger signals and a clinical indication of inflammation. The biological functions of SAA in inflammation have not been fully defined, although recent reports indicate that SAA induces proinflammatory cytokine expression. We now show that TLR2 is a functional receptor for SAA. HeLa cells expressing TLR2 responded to SAA with potent activation of NF-{kappa}B, which was enhanced by TLR1 expression and blocked by the Toll/IL-1 receptor/resistance (TIR) deletion mutants of TLR1, TLR2, and TLR6. SAA stimulation led to increased phosphorylation of MAPKs and accelerated I{kappa}B{alpha} degradation in TLR2-HeLa cells, and results from a solid-phase binding assay showed SAA interaction with the ectodomain of TLR2. Selective reduction of SAA-induced gene expression was observed in tlr2–/– mouse macrophages compared with wild-type cells. These results suggest a potential role for SAA in inflammatory diseases through activation of TLR2.

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 National Institutes of Health Grants AI040176 and GM066182 (to R.D.Y.).

2 Address correspondence and reprint requests to Dr. Richard D. Ye, University of Illinois at Chicago, 835 South Wolcott Avenue, M/C 868, Chicago, IL 60612. E-mail address: yer{at}uic.edu

3 Abbreviations used in this paper: SAA, serum amyloid A; CHO, Chinese hamster ovary (cell line); FPRL1, formyl peptide receptor-like 1; LTA, lipoteichoic acid; Pam3CSK4, (S)-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, 3HCl; PGN, peptidoglycan; TIR, Toll/IL-1 receptor/resistance.




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