Browse > Article
http://dx.doi.org/10.5352/JLS.2011.21.1.36

Glycated Serum Albumin Induces Interleukin-6 Expression in Vascular Smooth Muscle Cells  

Baek, Seung-Il (Department of Pharmacology, School of Medicine-Pusan National University)
Rhim, Byung-Yong (Department of Pharmacology, School of Medicine-Pusan National University)
Kim, Koan-Hoi (Department of Pharmacology, School of Medicine-Pusan National University)
Publication Information
Journal of Life Science / v.21, no.1, 2011 , pp. 36-43 More about this Journal
Abstract
Diabetes mellitus is associated with vascular complications. Diabetic patients exhibit high levels of glycated adducts in serum compared to non-diabetic individuals. The aim of this study was to investigate whether extracellular glycated albumin (GA) predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells (AoSMCs) to GA not only enhanced interleukin-6 (IL-6) release but also activated promoter activity of the IL-6 gene. GA-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-2 and TIR-domain-containing adapter-inducing interferon-$\beta$ (TRIF). Extracellular signal-regulated kinase (ERK) inhibition and diphenyleneiodium (DPI) also attenuated IL-6 induction by GA. Mutation at the nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-binding site in the IL-6 promoter region suppressed promoter activation in response to GA. The present study proposes that GA would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4, EKR, and NF-${\kappa}B$ play active roles in the process.
Keywords
Interleukin-6 (IL-6); glycated serum albumin; vascular smooth muscle cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Hattori, Y., H. Kakishita, K. Akimoto, M. Matsumura, and K. Kasai. 2001. Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C. Biochem. Biophys. Res. Commun. 281, 891-896.   DOI
2 Hattori, Y., M. Suzuki, S. Hattori, and K. Kasai. 2002. Vascular smooth muscle cell activation by glycated albumin (Amadori adducts). Hypertension 39, 22-28.   DOI
3 Akira, S. and K. Takeda. 2004. Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499-511.   DOI
4 Brownlee, M. 2001. Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813-820.   DOI
5 Zernecke, A., E. Shagdarsuren, and C. Weber. 2008. Chemokines in atherosclerosis: an update. Arterioscler. Thromb. Vasc. Biol. 28, 1897-1908.   DOI
6 Yang, X., D. Coriolan, V. Murthy, K. Schultz, D. T. Golenbock, and D. Beasley. 2005. Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling. Am. J. Physiol. Heart Circ. Physiol. 289, H1069-1076.   DOI
7 Yang, X., D. Coriolan, K. Schultz, D. T. Golenbock, and D. Beasley. 2005b. Toll-like receptor 2 mediates persistent chemokine release by Chlamydia pneumoniae-infected vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 25, 2308-2314.   DOI
8 Yang, X., V. Murthy, K. Schultz, J. B. Tatro, K. A. Fitzgerald, and D. Beasley. 2006. Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 291, H2334-2343.   DOI
9 Zuany-Amorim, C., J. Hastewell, and C. Walker. 2002. Toll-like receptors as potential therapeutic targets for multiple diseases. Nat. Rev. Drug Discov. 1, 797-807.   DOI
10 Michelsen, K. S., M. H. Wong, P. K. Shah, W. Zhang, J. Yano, T. M. Doherty, S. Akira, T. B. Rajavashisth, and M. Arditi. 2004. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc. Natl. Acad. Sci. U.S.A. 101, 10679-10684.   DOI
11 Ross, R. 1986. The pathogenesis of atherosclerosis-an update. N. Engl. J. Med. 314, 488-500.   DOI
12 Salazar, R., R. Brandt, and S. Krantz. 1995. Expression of fructosyllysine receptors on human monocytes and monocyte- like cell lines. Biochim. Biophys. Acta. 1266, 57-63.   DOI
13 Singh, R., A. Barden, T. Mori, and L. Beilin. 2001. Advanced glycation end-products: a review. Diabetologia 44, 129-146.   DOI
14 Sun, H. N., S. U. Kim, M. S. Lee, S. K. Kim, J. M. Kim, M. Yim, D. Y. Yu, and D. S. Lee. 2008. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of phosphoinositide 3-kinase and p38 mitogenactivated protein kinase signal pathways is required for lipopolysaccharide-induced microglial phagocytosis. Biol. Pharm. Bull. 31, 1711-1715.   DOI
15 Herder, C., B. Haastert, S. Muller-Scholze, W. Koenig, B. Thorand, R. Holle, H. E. Wichmann, W. A. Scherbaum, S. Martin, and H. Kolb. 2005. Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes 54, S11-17.   DOI
16 Wu, V. Y. and M. P. Cohen. 1995. Evidence for a ligand receptor system mediating the biologic effects of glycated albumin in glomerular mesangial cells. Biochem. Biophys. Res. Commun. 207, 521-528.   DOI
17 Wu, V. Y., C. W. Shearman, and M. P. Cohen. 2001. Identification of calnexin as a binding protein for Amadori-modified glycated albumin. Biochem. Biophys. Res. Commun. 284, 602-606.   DOI
18 Wu, Y. M., D. R. Robinson, and H. J. Kung. 2004. Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells. Cancer Res. 64, 7311-7320.   DOI
19 Higai, K., A. Shimamura, and K. Matsumoto. 2006. Amadori-modified glycated albumin predominantly induces E-selectin expression on human umbilical vein endothelial cells through NADPH oxidase activation. Clin. Chim. Acta. 367, 137-143.   DOI
20 Higgins, P. J. and H. F. Bunn. 1981. Kinetic analysis of the nonenzymatic glycosylation of hemoglobin. J. Biol. Chem. 256, 5204-5208.
21 Hollestelle, S. C., M. R. De Vries, J. K. Van Keulen, A. H. Schoneveld, A. Vink, C. F. Strijder, B. J. Van Middelaar, G. Pasterkamp, P. H. Quax, and D. P. De Kleijn. 2004. Toll-like receptor 4 is involved in outward arterial remodeling. Circulation 109, 393-398.   DOI
22 Kawai, T. and S. Akira. 2005. Toll-like receptor downstream signaling. Arthritis Res. Ther. 7, 12-19.   DOI
23 Libby, P. 2002. Inflammation in atherosclerosis. Nature 420, 868-874.   DOI
24 Bunn, H. F., K. H. Gabbay, and P. M. Gallop. 1978. The glycosylation of hemoglobin: relevance to diabetes mellitus. Science 200, 21-27.   DOI
25 Libby, P., P. M. Ridker, and A. Maseri. 2002. Inflammation and atherosclerosis. Circulation 105, 1135-1143.   DOI
26 Mansour, S. J., W. T. Matten, A. S. Hermann, J. M. Candia, S. Rong, K. Fukasawa, G. F. Vande Woude, and N. G. Ahn. 1994. Transformation of mammalian cells by constitutively active MAP kinase. Science 265, 966-970.   DOI
27 Medzhitov, R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1, 135-145.   DOI
28 Clements, R. S., Jr., W. G. Robison, Jr., and M. P. Cohen. 1998. Anti-glycated albumin therapy ameliorates early retinal microvascular pathology in db/db mice. J. Diabetes Complications 12, 28-33.   DOI
29 Cohen, M. P., R. S. Clements, J. A. Cohen, and C. W. Shearman. 1996. Glycated albumin promotes a generalized vasculopathy in the db/db mouse. Biochem. Biophys. Res. Commun. 218, 72-75.   DOI
30 Derijard, B., J. Raingeaud, T. Barrett, I. H. Wu, J. Han, R. J. Ulevitch, and R. J. Davis. 1995. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267, 682-685.   DOI   ScienceOn
31 Edfeldt, K., J. Swedenborg, G. K. Hansson, and Z. Q. Yan. 2002. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105, 1158-1161.
32 Eickelberg, O., M. Roth, R. Mussmann, J. J. Rudiger, M. Tamm, A. P. Perruchoud, and L. H. Block. 1999. Calcium channel blockers activate the interleukin-6 gene via the transcription factors NF-IL6 and NF-kappaB in primary human vascular smooth muscle cells. Circulation 99, 2276-2282.   DOI   ScienceOn