Browse > Article
http://dx.doi.org/10.4110/in.2009.9.3.90

The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-${\kappa}B$ in Macrophages: Implication for Atherosclerosis  

Kim, Ju-Young (The School of Life Sciences and Biotechnology, Kyungpook National University)
Kim, Won-Jung (The School of Life Sciences and Biotechnology, Kyungpook National University)
Kim, Ho (The School of Life Sciences and Biotechnology, Kyungpook National University)
Suk, Kyoung-Ho (Department of Pharmacology, School of Medicine, Kyungpook National University)
Lee, Won-Ha (The School of Life Sciences and Biotechnology, Kyungpook National University)
Publication Information
IMMUNE NETWORK / v.9, no.3, 2009 , pp. 90-97 More about this Journal
Abstract
Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation. Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface. Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-${\kappa}B$. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of $I{\kappa}B$, and nuclear translocation of NF-${\kappa}B$ p65 and p50 subunits. Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.
Keywords
macrophage; atherosclerosis; inflammation; CD147; cyclophilin A;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, Nabeshima K: The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res 55;434-439, 1995   PUBMED
2 Biswas C: Tumor cell stimulation of collagenase production by fibroblasts. Biochem Biophys Res Commun 109;1026-1034, 1982   DOI   PUBMED   ScienceOn
3 Kataoka H, DeCastro R, Zucker S, Biswas C: Tumor cell-derived collagenase-stimulatory factor increases expression of interstitial collagenase, stromelysin, and 72-kDa gelatinase. Cancer Res 53;3154-3158, 1993
4 Foda HD, Rollo EE, Drews M, Conner C, Appelt K, Shalinsky DR, Zucker S: Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN: attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340). Am J Respir Cell Mol Biol 25;717-724, 2001   DOI   PUBMED   ScienceOn
5 Major TC, Liang L, Lu X, Rosebury W, Bocan TM: Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma. Arterioscler Thromb Vasc Biol 22;1200-1207, 2002   DOI   ScienceOn
6 Damsker JM, Okwumabua I, Pushkarsky T, Arora K, Bukrinsky MI, Constant SL: Targeting the chemotactic function of CD147 reduces collagen-induced arthritis. Immunology 126;55-62, 2009
7 Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF: Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death. Diabetes 50;77-82, 2001   DOI   ScienceOn
8 Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K: Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 26;171-176, 1980   DOI   PUBMED
9 Ruggeri ZM: Structure and function of von Willebrand factor. Thromb Haemost 82;576-584, 1999   PUBMED
10 Whincup PH, Danesh J, Walker M, Lennon L, Thomson A, Appleby P, Rumley A, Lowe GD: von Willebrand factor and coronary heart disease: prospective study and meta-analysis. Eur Heart J 23;1764-1770, 2002   DOI   ScienceOn
11 Yang F, Tang E, Guan K, Wang CY: IKK beta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide. J Immunol 170;5630-5635, 2003   DOI   PUBMED
12 Konttinen YT, Li TF, Mandelin J, Liljestrom M, Sorsa T, Santavirta S, Virtanen I: Increased expression of extracellular matrix metalloproteinase inducer in rheumatoid synovium. Arthritis Rheum 43;275-280, 2000   DOI   ScienceOn
13 Sameshima T, Nabeshima K, Toole BP, Yokogami K, Okada Y, Goya T, Koono M, Wakisaka S: Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas. Int J Cancer 88;21-27, 2000   DOI   ScienceOn
14 Heidinger M, Kolb H, Krell HW, Jochum M, Ries C: Modulation of autocrine TNF-alpha-stimulated matrix metalloproteinase 9 (MMP-9) expression by mitogen-activated protein kinases in THP-1 monocytic cells. Biol Chem 387;69-78, 2006   DOI   ScienceOn
15 Sherry B, Yarlett N, Strupp A, Cerami A: Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. Proc Natl Acad Sci U S A 89;3511-3515, 1992   DOI   ScienceOn
16 Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med 340;115-126, 1999   DOI   ScienceOn
17 Nabeshima K, Lane WS, Biswas C: Partial sequencing and characterization of the tumor cell-derived collagenase stimulatory factor. Arch Biochem Biophys 285;90-96, 1991   DOI   ScienceOn
18 Shackel NA, McGuinness PH, Abbott CA, Gorrell MD, McCaughan GW: Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression. Am J Pathol 160;641-654, 2002   DOI   PUBMED   ScienceOn
19 Schmidt R, Bultmann A, Ungerer M, Joghetaei N, Bulbul O, Thieme S, Chavakis T, Toole BP, Gawaz M, Schomig A, May AE: Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase activity in cardiovascular cells: implications in acute myocardial infarction. Circulation 113;834-841, 2006   DOI   ScienceOn
20 Kim SH, Kang YJ, Kim WJ, Woo DK, Lee Y, Kim DI, Park YB, Kwon BS, Park JE, Lee WH: TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Circ J 68;396-399, 2004   DOI   ScienceOn
21 Pushkarsky T, Zybarth G, Dubrovsky L, Yurchenko V, Tang H, Guo H, Toole B, Sherry B, Bukrinsky M: CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A. Proc Natl Acad Sci U S A 98;6360-6365, 2001   DOI   ScienceOn
22 Kasinrerk W, Fiebiger E, Stefanova I, Baumruker T, Knapp W, Stockinger H: Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule. J Immunol 149;847-854, 1992   PUBMED
23 Caudroy S, Polette M, Nawrocki-Raby B, Cao J, Toole BP, Zucker S, Birembaut P: EMMPRIN-mediated MMP regulation in tumor and endothelial cells. Clin Exp Metastasis 19;697-702, 2002   DOI   ScienceOn
24 Spinale FG, Coker ML, Heung LJ, Bond BR, Gunasinghe HR, Etoh T, Goldberg AT, Zellner JL, Crumbley AJ: A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation 102;1944-1949, 2000   DOI   PUBMED   ScienceOn
25 Bae EM, Kim WJ, Suk K, Kang YM, Park JE, Kim WY, Choi EM, Choi BK, Kwon BS, Lee WH: Reverse signaling initiated from GITRL induces NF-kappaB activation through ERK in the inflammatory activation of macrophages. Mol Immunol 45;523-533, 2008   DOI   ScienceOn
26 Yang H, Li M, Chai H, Yan S, Lin P, Lumsden AB, Yao Q, Chen C: Effects of cyclophilin A on cell proliferation and gene expressions in human vascular smooth muscle cells and endothelial cells. J Surg Res 123;312-319, 2005   DOI   ScienceOn
27 Yurchenko V, O'Connor M, Dai WW, Guo H, Toole B, Sherry B, Bukrinsky M: CD147 is a signaling receptor for cyclophilin B. Biochem Biophys Res Commun 288;786-788, 2001   DOI   ScienceOn
28 Jin ZG, Lungu AO, Xie L, Wang M, Wong C, Berk BC: Cyclophilin A is a proinflammatory cytokine that activates endothelial cells. Arterioscler Thromb Vasc Biol 24;1186-1191, 2004   DOI   ScienceOn
29 Jin ZG, Melaragno MG, Liao DF, Yan C, Haendeler J, Suh YA, Lambeth JD, Berk BC: Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 87;789-796, 2000   DOI   PUBMED   ScienceOn
30 Schmidt R, Bultmann A, Fischel S, Gillitzer A, Cullen P, Walch A, Jost P, Ungerer M, Tolley ND, Lindemann S, Gawaz M, Schomig A, May AE: Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on platelets, activates platelets, and augments nuclear factor kappaB-dependent inflammation in monocytes. Circ Res 102;302-309, 2008   DOI   ScienceOn
31 Kim SH, Lessner SM, Sakurai Y, Galis ZS: Cyclophilin A as a novel biphasic mediator of endothelial activation and dysfunction. Am J Pathol 164;1567-1574, 2004   DOI   PUBMED   ScienceOn
32 Yang H, Chen J, Yang J, Qiao S, Zhao S, Yu L: Cyclophilin A is upregulated in small cell lung cancer and activates ERK1/2 signal. Biochem Biophys Res Commun 361;763-767, 2007   DOI   ScienceOn
33 Kim H, Kim WJ, Jeon ST, Koh EM, Cha HS, Ahn KS, Lee WH: Cyclophilin A may contribute to the inflammatory processes in rheumatoid arthritis through induction of matrix degrading enzymes and inflammatory cytokines from macrophages. Clin Immunol 116;217-224, 2005   DOI   ScienceOn
34 Damsker JM, Bukrinsky MI, Constant SL: Preferential chemotaxis of activated human CD4+ T cells by extracellular cyclophilin A. J Leukoc Biol 82;613-618, 2007   DOI   ScienceOn
35 Yang Y, Lu N, Zhou J, Chen ZN, Zhu P: Cyclophilin A up-regulates MMP-9 expression and adhesion of monocytes/macrophages via CD147 signalling pathway in rheumatoid arthritis. Rheumatology (Oxford) 47;1299-1310, 2008   DOI   ScienceOn
36 Ellis SM, Nabeshima K, Biswas C: Monoclonal antibody preparation and purification of a tumor cell collagenase- stimulatory factor. Cancer Res 49;3385-3391, 1989   PUBMED
37 Kamei M, Yoneda K, Kume N, Suzuki M, Itabe H, Matsuda K, Shimaoka T, Minami M, Yonehara S, Kita T, Kinoshita S: Scavenger receptors for oxidized lipoprotein in age-related macular degeneration. Invest Ophthalmol Vis Sci 48;1801-1807, 2007   DOI   ScienceOn
38 Pilarczyk K, Sattler KJ, Galili O, Versari D, Olson ML, Meyer FB, Zhu XY, Lerman LO, Lerman A: Placenta growth factor expression in human atherosclerotic carotid plaques is related to plaque destabilization. Atherosclerosis 196;333-340, 2008   DOI   ScienceOn
39 Libby P: Atherosclerosis in Inflammation. Nature 420;868-874, 2002   DOI   PUBMED   ScienceOn
40 Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P, Bugelski P, Yan L: Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res 65;3193-3199, 2005   DOI   PUBMED
41 Zhong H, May MJ, Jimi E, Ghosh S: The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 9;625-636, 2002   DOI   ScienceOn
42 Lee WH, Kim SH, Lee Y, Lee BB, Kwon B, Song H, Kwon BS, Park JE: Tumor necrosis factor receptor superfamily 14 is involved in atherogenesis by inducing proinflammatory cytokines and matrix metalloproteinases. Arterioscler Thromb Vasc Biol 21;2004-2010, 2001   DOI   ScienceOn
43 Boulos S, Meloni BP, Arthur PG, Majda B, Bojarski C, Knuckey NW: Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury. Neurobiol Dis 25;54-64, 2007   DOI   ScienceOn