Regulatory Effects of High Glucose on the Expression of Toll-Like Receptor Gene and Cytokine Production in Human Peripheral-Blood Mononuclear Cells

Article Preview

Abstract:

To investigate the regulatory effects of high glucose on the expression of Toll Like Receptor(TLR) Gene and the level of tumor necrosis factor(TNF)-α and interleukin(IL) -6 in human peripheral-blood mononuclear cells . Methods The alterations of TLR1~10 mRNA expression in human peripheral-blood mononuclear cells were quantitated using real-time quantitative-polymerasechain reaction. The level of TNF-α and IL-6 were measured by Enzyme-Linked Immuno Sorbent Assay . The anti-TLRmAb were used to block the mononuclear cells 30 min, high glucose was used to stimulate the cells. Rusults high glucose strongly up-regulated the expression of TLR3、5 mRNA but the expression of the other sub-TLRs weren’t changed .The concentrations of TNF-α、IL-6 were 86.40±8.46 and 874.66±92.84 in high glucose group, all significantly higher than that the control experiment (60.49±6.80 and 541.80±81.08 , all P<0.01), The anti-TLR3mAb and anti-TLR5mAb were used to block the mononuclear cells , The concentrations of TNF-α、IL-6 (72.41±8.52 and 700.59±84.88) were lower than that in the high glucose group, all P<0.05 . Conclusion high glucose may be endogenous ligand of TLRs and high glucose can regulate the release of inflammation cytokines from human peripheral-blood mononuclear cells through TLR signal way.

You might also be interested in these eBooks

Info:

Periodical:

Advanced Materials Research (Volumes 179-180)

Pages:

374-379

Citation:

Online since:

January 2011

Export:

Price:

Permissions CCC:

Permissions PLS:

Сopyright:

© 2011 Trans Tech Publications Ltd. All Rights Reserved

Share:

Citation:

[1] Kathryn E, Wellen , Gokhan S, etal. Inflammation, stress and diabetes[J]. J Clin invest, 2005, 115: 1111-1119.

Google Scholar

[2] Hansson GK, Libby P, Schonbeck U, etal. Innate and adaptive immunity in the pathogenesis of atherosclerosis[J]. Circ Res, 2002, 91: 281-291.

Google Scholar

[3] Sowers JR, Stump CS. Insights into the biology of diabetic vascular disease: what's new?[J]. Am J Hypertens, 2004, 17: 2-6.

Google Scholar

[4] Oude Nijhuis CS, Vellenga E, Daenen SM, etal. Endothelial cells are main producers of interleukin-8 through Toll-like receptor 2 and 4 signaling during bacterial infection in leukopenic cancer patients[J]. Clin Diagn Lab Immunol, 2003, 10: 558-563.

DOI: 10.1128/cdli.10.4.558-563.2003

Google Scholar

[5] Goraya TY, Leibson CL, Palumbo PJ , et al. Coronary atherosclerosis in diabetes mellitus. A population-based autopsy study [J]. J Am Coll Cardiol, 2002, 40: 946-953.

Google Scholar

[6] Ledru F, Ducimetiere P, Battaglia S, et al. New diagnostic criteria for diabetes and coronary artery disease: Insights from an angiographic study[J]. J Am Coll Cardiol, 2001, 37: 1543-1550.

DOI: 10.1016/s0735-1097(01)01183-4

Google Scholar

[7] Forbes JM, Yee LT, Thallas V, etal. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis[J]. Diabetes, 2004, 53: 1813-1823.

DOI: 10.2337/diabetes.53.7.1813

Google Scholar

[8] Veiraiah A. Hyperglycemia, lipoprotein glycation, and vascular disease[J].  Angiology, 2005, 56: 431-487.

DOI: 10.1177/000331970505600411

Google Scholar

[9] Libby P. Inflammation in atherosclerosis [J]. Nature, 2002, 420: 868-874.

Google Scholar

[10] Bucciarelli LG, Wendt T, Qu W, etal. RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E null mice [J]. Circulation, 2002, 106: 2 827-2835.

DOI: 10.1161/01.cir.0000039325.03698.36

Google Scholar

[11] Joy SV, Scates AC, Bearelly S, etal. Ruboxistaurin, a protein kinase C beta inhibitor, as an emerging treatment for diabetes microvascular complications [J].  Ann Pharmacol Ther, 2005, 39: 1693-1699.

DOI: 10.1345/aph.1e572

Google Scholar

[12] Sonta T, Inoguchi T, Tsubouchi H, etal. Evalution of oxidative stress in diabetic animals by in vivo electron spin resonance measurement role of protein kinase C [J]. Diab Res Clin Prac, 2004, 66: 109-113.

DOI: 10.1016/j.diabres.2004.05.008

Google Scholar

[13] Scivittaro V, Ganz MB, Weiss MF. AGE induce oxidative stress and activate protein kinase C-beta (Ⅱ) in neonatal mesangial cells [J]. Am J Physiol Renal Physiol, 2000, 278: 676-683.

DOI: 10.1152/ajprenal.2000.278.4.f676

Google Scholar

[14] Song MJ, Kim KH, Yoon JM, etal. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes[J]. Biochem Biophys Res Commun, 2006, 346: 739-745.

DOI: 10.1016/j.bbrc.2006.05.170

Google Scholar

[15] Pirie FJ, Pegoraro R, Motala AA, etal. Toll-like receptor 3 gene polymorphisms in South African Blacks with type 1 diabetes[J]. Tissue Antigens, 2005, 66: 125-130.

DOI: 10.1111/j.1399-0039.2005.00454.x

Google Scholar

[16] Santin I, Bilbao JR, de Nanclares GP, etal. No association of TLR2 and TLR4 polymorphisms with type I diabetes mellitus in the Basque population[J]. Ann N Y Acad Sci, 2006, 1079: 268-272.

DOI: 10.1196/annals.1375.040

Google Scholar

[17] Schreyer SA, Vick CM, Boeuf RC, etal. Loss of lymphotoxi-α but not tumor necrosis factor-α reduces atherosclerosis in mice[J]. J Biol Chem, 2002, 277: 12364-12368.

DOI: 10.1074/jbc.m111727200

Google Scholar

[18] Rudkin JS, Stehouwer C, Coppack SW, etal. C-reactive protein in healthy subjects-associations with obesity insulin resistance and endothelial dysfunction . A potential role for cytokines originating from adipose tissue[J]. Art Thromb Vasc Biol, 1999, 19: 972-978.

DOI: 10.1161/01.atv.19.4.972

Google Scholar

[19] Romano M, Sironi M, Toniatti C, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment[J]. Immunity, 1997, 6: 13-20.

DOI: 10.1016/s1074-7613(00)80334-9

Google Scholar

[20] Steven E, Shoelson, Jongsoon Lee, et al. Inflammation and insulin resistance [J]. J Clin Invest. 2006, 116: 1793–1801.

Google Scholar

[21] Sherry CL, O'Connor JC, Kramer JM, etal. Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p.38 MAPK. J Immunol. 2007, 15; 178: 663-70.

DOI: 10.4049/jimmunol.178.2.663

Google Scholar