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The role of CD40 receptor-ligand system in the development of diabetes mellitus and its complications

Abstract

The CD40 receptor-CD40 ligand system, along with other signal molecules, plays an important role in the development of immune and inflammatoryreactions. CD40R and CD40L are expressed in lymphocytes, monocytes, platelets, endothelial and smooth muscle cells, pancreatic beta-cells, adipocytes,and other cells. The CD40-CD40L system participates in the formation of immune and inflammatory reactions in the cardiovascular system,platelet production and development of autoimmune diseases. Signals mediated through CD40 receptors are involved in the autoimmune process intype 1 diabetes, inflammation of adipose tissue in DM2, development of atherosclerosis and diabetic nephropathy. Therefore, the CD40-CD40Lsystem can be regarded as a universal pathogenetic factor responsible for immune and inflammatory processes, hyperglycemia, and vascular complications.Measurement of CD40 expression in lymphocytes, monocytes, and adipocytes and sCD40L in blood and urine can be used to diagnose andforetell immune and inflammatory processes associated with diabetes mellitus. HMG-CoA reductase inhibitors (statins) and disaggregants (aspirin,clopidogrel) inhibit activity of the CD40-CD40L system. Further studies of possibilities of pharmacological correction of this system may provide abasis for the development of new therapeutic modalities for the management of diabetes and its complications.

About the Authors

Irina Arkad'evna Bondar'
Novosibirsk State Medical University, Novosibirsk


Vadim Valer'evich Klimontov
Novosibirsk State Medical University, Novosibirsk


References

1. Eizirik D.L., Colli M.L., Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes // Nat. Rev. Endocrinol. - 2009. - № 5 (4). - Р. 219-226.

2. Бондарь И.А., Климонтов В.В. Иммуновоспалительные механизмы в формировании диабетической нефропатии // Проблемы эндокри- нологии. - 2007. - № 2. - C. 34-40.

3. Fornoni A., Ijaz A., Tejada T., Lenz O. Role of inflammation in diabetic nephropathy // Curr. Diabetes Rev. - 2008. - № 4 (1). - Р. 10-17.

4. Ray A., Huisman M.V., Tamsma J.T. et al. The role of inflammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus // Eur. J. Intern. Med. - 2009. - № 20 (3). - Р. 253-260.

5. Schönbeck U., Libby P. The CD40/CD154 receptor/ligand dyad // Cell Mol. Life Sci. - 2001. - № 58. - Р. 4-43.

6. van Kooten C., Banchereau J. CD40-CD40 ligand. J. Leukoc // Biol. - 2000. - № 67. - Р. 2-17.

7. Wagner D.H.Jr., Vaitaitis G., Sanderson R. et al. Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes // Proc. Natl. Acad. Sci. USA. - 2002. - № 99 (6). - Р. 3782-3787.

8. Waid D.M., Wagner R.J., Putnam A. et al. A unique T cell subset described as CD4loCD40+ T cells (TCD40) in human type 1 diabetes // Clin. Immunol. - 2007. - № 124 (2). - Р. 138-148.

9. Jinchuan Y., Zonggui W., Jinming C. et al. Upregulation of CD40-CD40 ligand system in patients with diabetes mellitus // Clin. Chim. Acta. - 2004. - № 339 (1-2). - Р. 85-90.

10. Cipollone F., Chiarelli F., Davi G., et al. Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control // Diabetologia. - 2005. - № 48 (6). - Р. 1216-1224.

11. Devaraj S., Glaser N., Griffen S. et al. Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes // Diabetes. - 2006. - № 55 (3). - Р. 774-779.

12. Katakami N., Kaneto H., Matsuhisa M. et al. Association of soluble CD40 ligand with carotid atherosclerosis in Japanese type 1 diabetic patients // Diabetologia. - 2006. - № 49 (7). - Р. 1670-1676.

13. Chatzigeorgiou A.E., Lembessis P.E., Mylona-Karagianni C.F. et al. CD40 expression and its association with low-grade inflammation in a Greek population of type 1 diabetic juveniles: evidence for differences in CD40 mRNA isoforms expressed by peripheral blood mononuclear cells // Exp. Clin. Endocrinol. Diabetes. - 2010. - № 118 (1). - Р. 38-46.

14. Klein D., barbe-Tuana F.M., Pugliese A. et al. A functional CD40 receptor is expressed in pancretic beta cells // Diabetologia. - 2005. - № 48 (2). - Р. 268-276.

15. Barbé-Tuana F.M., Klein D., Ichii H. et al. CD40-CD40 ligand interaction activates proinflammatory pathways in pancreatic islets // Diabetes. - 2006. - № 55 (9). - Р. 2437-2445.

16. Klein D., Timoneri F., Ichii H. et al. CD40 activation in human pancreatic islets and ductal cells // Diabetologia. - 2008. - № 51 (10). - Р. 1853-1861.

17. Waid D.M., Vaitaitis G.M., Wagner D.H. Jr. Peripheral CD4loCD40+ auto-aggressive T cell expansion during insulin-dependent diabetes mellitus // Eur. J. Immunol. - 2004. - № 34 (5). - Р. 1488-1497.

18. Nanji S.A., Hancock W.W., Luo B. et al. Costimulation blockade of both inducible costimulator and CD40 ligand induces dominant tolerance to islet allografts and prevents spontaneous autoimmune diabetes in the NOD mouse // Diabetes. - 2006. - № 55 (1). - Р. 27-33.

19. Balasa B., Krahl T., Patstone G. et al. CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice // J. Immunol. - 1997. - № 159 (9). - Р. 4620-4627.

20. Every A.L., Kramer D.R., Mannering S.I. et al. Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes // J. Immunol. - 2006. - № 176 (8). - Р. 4608-4615.

21. Li G., Sanders J.M., Bevard M.H. et al. CD40 ligand promotes Mac-1 expression, leukocyte recruitment, and neointima formation after vascular injury // Am. J. Pathol. - 2008. - № 172 (4). - Р. 1141-1152.

22. Kover K.L, Geng Z., Hess D.M. et al. Anti-CD154 (CD40L) prevents recurrence of diabetes in islet isografts in the DR-BB rat // Diabetes. - 2000. - № 49 (10). - Р. 1666-1670.

23. Шевченко О.П., Природова О.Ф., Орлова О.В., Шевченко А.О. CD40 лиганд у больных ишемической болезнью сердца в сочетании с сахарным диабетом 2 типа // Российский кардиологический журнал. - 2006. - № 5. - С. 23-28.

24. Bláha V., Andrýs C., Smahelová A. et al. Effect of atorvastatin on soluble CD14, CD40 Ligand, sEand sP-selectins and MCP-1 in patients with type 2 diabetes mellitus: relationship to cholesterol turnover // Pharmacol. Res. - 2006. - № 54 (6). - Р. 421-428.

25. Gokulakrishnan K., Deepa R., Mohan V., Gross M.D. Soluble Pselectin and CD40L levels in subjects with prediabetes, diabetes mellitus, and metabolic syndrome-the Chennai Urban Rural Epidemiology Study // Metabolism. - 2006. - № 55 (2). - Р. 237-242.

26. Santini E., Lupi R., Baldi S. et al. Effects of different LDL particles on inflammatory molecules in human mesangial cells // Diabetologia. - 2008. - № 51 (11). - Р. 2117-2225.

27. Unek I.T., Bayraktar F., Solmaz D. et al. Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome // Metabolism. - 2010. - № 59 (3). - Р. 305-313.

28. Vaidyula V.R., Rao A.K., Mozzoli M. et al. Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand // Diabetes. - 2006. - № 55 (1). - Р. 202-208.

29. Varo N., Libby P., Nuzzo R. et al. Elevated release of sCD40L from platelets of diabetic patients by thrombin, glucosee and advanced glycation end products // Diab. Vasc. Dis. Res. - 2005. - № 2 (2). - Р. 81-87.

30. Oliver S.R., Flores R.L., Pontello A.M. et al. Acute suppression of circulating sCD40L during hyperglycemia and euglycemic-hyperinsulinemia in healthy young males // J. Investig. Med. - 2008. - № 56 (7). - Р. 902-910.

31. Penno G., Pucci L., Dell'Omo G. et al. Soluble CD40 ligand levels in essential hypertensive men: evidence of a possible role of insulin resistance // Am. J. Hypertens. - 2009. - № 22 (9). - Р. 1007-1013.

32. Шварц В. Воспаление жировой ткани. Часть 2. Патогенетическая роль при сахарном диабете 2 типа // Пробл. Эндокринол. - 2009. - № 55 (5). - С. 43-48.

33. Poggi M., Jager J., Paulmyer-Lacroix O. et al. The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes // Diabetologia. - 2009. - № 52 (6). - Р. 1152-1163.

34. Missiou A., Wolf D., Platzer I. et al. CD40L induces inflammation and adipogenesis in adipose cells-a potential link between metabolic and cardiovascular disease // Thromb. Haemost. - 2010. - № 103 (4). - Р. 788-796.

35. Cabeza N., Li Z., Schulz C. et al. Surface expression of collagen receptor Fc receptor-gamma/glycoprotein VI is enhanced on platelets in type 2 diabetes and mediates release of CD40 ligand and activation of endothelial cells // Diabetes. - 2004. - № 53 (8). - Р. 2117-2221.

36. Rizvi M., Pathak D., Freedman J.E., Chakrabarti S. CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease // Trends Mol. Med. - 2008. - № 14 (12). - Р. 530-538.

37. Chai H., Aghaie K., Zhou W. Soluble CD40 ligand induces human coronary artery smooth muscle cells proliferation and migration // Surgery. - 2009. - № 146 (1). - Р. 5-11.

38. Шевченко О.П., Природова О.Ф., Шевченко А.О. Клиническое значение растворимого CD40 лиганда у больных ишемической болезнью сердца // Кардиоваскулярная терапия и профилактика. - 2006. - № 7. - С. 101-111.

39. Александрова Е.Н., Новиков А.А., Насонов Е.Л. Растворимый лиганд CD40 при аутоиммунных заболеваниях и атеросклерозе // Тер. архив. - 2005. - № 12. - С. 91-95.

40. Davì G., Tuttolomondo A., Santilli F. et al. CD40 ligand and MCP-1 as predictors of cardiovascular events in diabetic patients with stroke // J. Atheroscler. Thromb. - 2009. - № 16 (6). - Р. 707-713.

41. Бондарь И. А., Климонтов В. В. Иммуновоспалительные механизмы в формировании диабетической нефропатии // Проблемы эндокри- нологии. - 2007. - № 2. - С. 34-40.

42. Бондарь И.А., Климонтов В.В. Патогенез диабетической нефропатии. Иммуновоспалительные факторы. // Сахарный диабет и хрониче- ская болезнь почек. /Под ред. М. В. Шестаковой, И. И. Дедова. - М.: Медицинское информационное агентство, 2009. - С. 109-118.

43. Yellin M.J., D'Agati V., Parkinson G. et al. Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides // Arthritis Rheum. - 1997. - № 40 (1). - Р. 124-134.

44. Starke A., Wüthrich R.P., Waeckerle-Men Y. TGF-beta treatment modulates PD-L1 and CD40 expression in proximal renal tubular epithelial cells and enhances CD8 cytotoxic T-cell responses // Nephron. Exp. Nephrol. - 2007. - № 107 (1). - Р. e22-е29.

45. Li H., Nord E.P. CD40/CD154 ligation induces mononuclear cell adhesion to human renal proximal tubule cells via increased ICAM-1 expression // Am. J. Physiol. Renal. Physiol. - 2005. - № 289 (1). - Р. F145-F153.

46. Li H., Nord E.P. CD40 ligation stimulates MCP-1 and IL-8 production, TRAF6 recruitment, and MAPK activation in proximal tubule cells // Am. J. Physiol. Renal. Physiol. - 2002. - № 282 (6). - Р. F1020-F1033.

47. Yngen M., Ostenson C.G., Hu H. et al. Enhanced P-selectin expression and increased soluble CD40 Ligand in patients with Type 1 diabetes mellitus and microangiopathy: evidence for platelet hyperactivity and chronic inflammation // Diabetologia. - 2004. - № 47 (3). - Р. 537-540.

48. Chiarelli F., Giannini C., Verrotti A. et al. Increased concentrations of soluble CD40 ligand may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria // Diabetes Metab. Res. Rev. - 2008. - № 24 (7). - Р. 570-576.

49. Jialal I., Miguelino E., Griffen S.C., Devaraj S. Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of inflammation with low-dose simvastatin therapy in patients with type 1 diabetes // J. Clin. Endocrinol. Metab. - 2007. - № 92 (8). - Р. 3136-3140.

50. Chu C.S., Lee K.T., Lee M.Y. et al. Effects of rosiglitazone alone and in combination with atorvastatin on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus // Am. J. Cardiol. - 2006. - № 97 (5). - Р. 646-650.

51. Schönbeck U., Gerdes N., Varo N. et al. Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L expression in human vascular cells // Circulation. - 2002. - № 106 (23). - Р. 2888-2893.

52. Ray D.M., Spinelli S.L., O'Brien J.J. et al. Platelets as a novel target for PPARgamma ligands: implications for inflammation, diabetes, and cardiovascular disease // BioDrugs. - 2006. - № 20 (4). - Р. 231-241.

53. Yener S., Comlekci A., Akinci B. et al. Soluble CD40 ligand, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor- 1-antigen in normotensive type 2 diabetic subjects without diabetic complications. Effects of metformin and rosiglitazone // Med. Princ. Pract. - 2009. - № 18 (4). - Р. 266-271.

54. Pfützner A., Marx N., Lübben G. et al. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study // J. Am. Coll. Cardiol. - 2005. - № 45 (12). - Р. 1925-1931.

55. Willerson J.T., Cable G., Yeh E.T., PROCLAIM Investigators. PROCLAIM: pilot study to examine the effects of clopidogrel on inflammatory markers in patients with metabolic syndrome receiving low-dose aspirin // Tex. Heart Inst. J. - 2009. - № 36 (6). - Р. 530-539.

56. Mena M.P., Sacanella E., Vazquez-Agell M. et al. Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet // Am. J. Clin. Nutr. - 2009. - № 89 (1). - Р. 248-256.


Review

For citations:


Bondar' I.A., Klimontov V.V. The role of CD40 receptor-ligand system in the development of diabetes mellitus and its complications. Diabetes mellitus. 2011;14(3):21-25. (In Russ.)

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