EFFECTS OF MEVALONATE PATHWAY MODULATORS UPON REACTIVITY OF MACROPHAGES IN E XPERIMENTAL NEPHROSCLEROSIS
https://doi.org/10.15789/1563-0625-2009-6-499-508
Abstract
Abstract. The effects of cholesterol (Ch) diet, i.p. administration of mevalonic acid (Mev) and their combined application upon nitric oxide (NO) production in peritoneal macrophages, as well as upon biochemical characteristics of kidney function derangements, and histological parameters of tissue alterations, infiltration and fibrosis were studied in experimental model of chronic rhabdomyolysis-induced renal injury induced in C57Bl/6 mice. The effects of Ch diet, Mev and their combination on the degree of renal fibrosis were also studied in a model of unilateral ureteral obstruction. In normal animals, and, especially, in nephrotic mice, Ch diet was shown to cause a dramatic decrease of LPS-induced NO production, whereas Mev did enhance NO production significantly. Administration of Mev during Ch treatment abolished, in part, the suppressive effect of Ch. Ch diet was shown to enhance fibrotic response, without significant effect upon tissue alteration and mononuclear infiltration, whereas Mev enhanced alterative component and slightly diminished fibrosis. We conclude that Ch diet and Mev exert opposite effects upon the course and outcome of chronic nephropathy for their inhibitory (Ch) and stimulating (Mev) effect on mevalonate pathway, which is involved in the control of macrophage M1-M2 polarization.
About the Authors
Ya. Sh. Schwarz
ГУ НИИ терапии СО РАМН, г. Новосибирск
Russian Federation
Russian Federation
S. N. Belogorodtsev
ГУ НИИ клинической иммунологии СО РАМН, г. Новосибирск
Russian Federation
Russian Federation
P. N. Filimonov
ФГУ Новосибирский НИИ туберкулеза МЗСР РФ, г. Новосибирск
Russian Federation
Russian Federation
G. V. Seledtsova
ГУ НИИ клинической иммунологии СО РАМН, г. Новосибирск
Russian Federation
Russian Federation
References
1. Маянский Д.Н., Шварц Я.Ш., Цырендоржиев Д.Д., Кутина С.Н. Функциональные перестройки системы мононуклеарных фагоцитов при экспериментальном циррозе печени // Бюлл. эксперим. биол. и мед. – 1988. – Т. 105. – № 2 – С. 214-216
2. Шварц Я.Ш., Душкин М.И., Комарова Н.И., Воронцова Е.В., Кузнецова И.С. Холестерининдуцированная стимуляция поствоспалительного гепатофиброза // Бюлл. эксперим. биол. и мед. – 2008. – Т. 145. – № 6. – С. 638-641.
3. Шварц Я.Ш., Хощенко О.М., Душкин М.И., Феофанова Н.А. Действие холестерина и агонистов ядерных гормональных рецепторов на продукцию трансформирующего фактора роста-бета (ТФР-β) в макрофагах // Бюлл. эксперим. биол. и мед. – 2009. – Т. 147.
4. Böttinger E.P., Bitzer M. TGF-β Signaling in Renal Disease // J. Am. Soc. Nephrol. – 2002. – Vol. 13. – P. 2600-2610.
5. Diamond J.R. Macrophages and progressive renal disease in experimental hydronephrosis // Am. J. Kidney Dis. – 1995. – Vol. 26. – P. 133-140.
6. Ding G., van Goor H., Frye J., Diamond J.R. Transforming growth factor-beta expression in macrophages during hypercholesterolemic states // Am. J. Physiol. – 1994. – Vol. 267. – P. 937-943.
7. Duffield J.S. The inflammatory macrophage: a story of Jekyll and Hyde // Clin. Sci. – 2003. – Vol.104. – P. 27-38.
8. Eddy A.A. Interstitial inflammation and fibrosis in rats with diet-induced hypercholesterolemia // Kidney Int. – 1996. – Vol. 50. – P. 1139-1149.
9. Eddy A.A. Interstitial fibrosis in hypercholesterolemic rats: role of oxidation, matrix synthesis, and proteolytic cascades // Kidney Int. – 1998. – Vol. 53. – P. 1182-1189.
10. Feingold K.R., Pollock A.S., Moser A.H., Shigenaga J.K., Grunfeld C. Discordant regulation of proteins of cholesterol metabolism during the acute phase response // J. Lipid Res. – 1995. – Vol. 36. – P. 1474-1482.
11. Ferenbach D., Kluth D.C., Hughes J. Inflammatory cells in renal injury and repair // Semin. Nephrol. – 2007. – Vol. 27. – P. 250-259.
12. Goerdt S., Orfanos C.E. Other functions, other genes: alternative activation of antigenpresenting cells // Immunity. – 1999. – Vol. 10. – P. 137-142.
13. Griess Reagent System Technical Bulletin TB229, Promega, 06/2005. – P. 1-7.
14. Hausmann E.H., Hao S.Y., Pace J.L., Parmely M.J. Transforming growth factor beta 1 and gamma interferon provide opposing signals to lipopolysaccharideactivated mouse macrophages // Infect. Immun. – 1994. – Vol. 62. – P. 3625-3632.
15. Huang K.C., Chen C.W., Chen J.C., Lin W.W. Statins induce suppressor of cytokine signaling-3 in macrophages // FEBS Lett. – 2003. – Vol. 555. – P. 385-389.
16. Huang K.C, Chen CW, Chen JC, Lin WW. HMG-CoA reductase inhibitors inhibit inducible nitric oxide synthase gene expression in macrophages // J. Biomed. Sci. – 2003. – Vol. 10. – P. 396-405.
17. Hwa J.J., Zollman S., Warden C.H., Taylor B.A., Edwards P.A., Fogelman A.M., Lusis A.J. Genetic and dietary interactions in the regulation of HMG-CoA reductase gene expression // J. Lipid Res. – 1992. – Vol. 33. – P. 711-725.
18. Ikezumi Y., Hurst L., Atkins R.C., Nikolic-Paterson D.J. Macrophage-mediated renal injury is dependent on signaling via the JNK pathway // J. Am. Soc. Nephrol. – 2004. – Vol. 15. – P. 1775 - 1784.
19. Jenke H-S., Lowel M., Berndt J. In Vivo Effect of Cholesterol Feeding on the Short Term Regulation of Hepatic Hydroxymethylglutaryl Coenzyme A Reductase during the Diurnal Cycle // J. Biol. Chem. – 1981. – Vol. 258. – P. 9622-9626.
20. Lieberthal W. and Nigam S.K. Acute renal failure. II. Experimental models of acute renal failure: imperfect but indispensable // Am. J. Physiol. Renal Physiol. –2000. – N 278. – P. F1-F120.
21. Lopez-de Leon, Rojkind M. A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections // J. Histochem. Cytochem. – 1985. – Vol. 33. – P. 737-743.
22. Lupher Jr M.L., Gallatin W.M. Regulation of fibrosis by the immune system // Adv. Immunol. – 2006. – Vol. 89. – P. 245-288.
23. Matsuno R., Aramaki Y., Tsuchiya S. Involvement of TGF-beta in inhibitory effects of negatively charged liposomes on nitric oxide production by macrophages stimulated with LPS // Biochem. Biophys. Res. Commun. – 2001. – Vol. 281. – P. 614-616.
24. Mayanski D.N., Schwartz Y.Sh., Kutina S.N., Zubakhin A.A., Mayanskaya N.N., Tsyrendorjiev D.D. Mononuclear phagocyte system responsiveness in CCl4-induced liver cirrhosis // Int. J. Exp. Path. – 1993. – Vol. 74. – P. 229-236.
25. Mills C.D., Kincaid K., Alt J.M., Heilman M.J., Annette M. H. M1/M2 macrophages and the Th1/Th2 paradigm // J. Immunol. – 2000. – Vol. 164. – P. 6166-6173.
26. Nath K.A., Balla G., Vercellotti G.N., Balla J., Jacob H.S., Levitt M.D., Rosenberg M.E. Induction of heme oxygenase is a rapid and protective response in rhabdomyolysis in the rat // J. Clin. Invest. – 1992. – Vol. 90. – P. 267-270.
27. Nishida M., Hamaoka K. Macrophage Phenotype and Renal Fibrosis in Obstructive Nephropathy // Nephron Exp. Nephrol. – 2008. – Vol. 110. – P. 31-36.
28. Pahan K., Sheikh F.G., Namboodiri A.M., Singh I. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages // J. Clin. Invest. – 1997. – Vol. 100. – P. 2671 - 2679.
29. Porreca E., Di Febbo C., Baccante G., Di Nisio M., Cuccurullo F. Increased transforming growth factor-beta(1) circulating levels and production in human monocytes after 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibition with pravastatin // J. Am. Coll. Cardiol. – 2002. – Vol. 39. – P. 1752-1757.
30. Rosenberger С., Goldfarb M., Shina A., Bachmann S., Frei U., Eckardt K. U., Schrader T., Rosen S., Heyman S.N. Evidence for sustained renal hypoxia and transient hypoxia adaptation in experimental rhabdomyolysis-induced acute kidney injury // Nephrol. Dial. Transplant. – 2008. – Vol. 23. – P. 1135-1143.
31. Salimuddin, Nagasaki A., Gotoh T., Isobe H., Mori M. Regulation of the genes for arginase isoforms and related enzymes in mouse macrophages by lipopolysaccharide // Am. J. Physiol. (Endocrinol. Metab.-40). – 1999. – Vol. 277. – P. 110-117.
32. Sato K., Miyakawa K., Takeya M., Hattori R., Yui Y., Sunamoto M., Ichimori Y., Ushio Y., Takahashi K. Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS // J. Leukoc. Biol. – 1995. – Vol. 57. – P. 36-44.
33. Saucier S.E., Kandutsch A.A., Gayen A.K., Swahn D.K., Spencer T.A. Oxysterol regulators of 3-hydroxy-3-methylglutaryl-CoA reductase in liver. Effect of dietary cholesterol // J. Biol. Chem. – 1989. – Vol. 264. – P. 6863-6869.
34. Song E., Ouyang N., Hörbelt M., Antus B., Wang M., Exton M.S. Influence of alternatively and classically activated macrophages on fibrogenic activities of human fibroblasts // Cell Immunol. – 2000. – Vol. 204. – P. 19-28.
35. Takaki H., Minoda Y., Koga K., Takaesu G., Yoshimura A., Kobayashi T. TGF-β1 suppresses IFNϒ-induced NO production in macrophages by suppressing STAT1 activation and accelerating iNOS protein degradation // Genes Cells. – 2006. – Vol. 11. – P. 871-882.
36. Ustundag S., Yalcin O., Sen S., Cukur Z., Ciftci S., Demirkan B. Experimental myoglobinuric acute renal failure: the effect of vitamin C // Ren. Fail. – 2008. – Vol. 30. – P. 727-735.
37. Waddington S.N., Tam F.W.K., Cook H.T., Cattell V. Arginase activity is modulated by IL-4 and HOArg in nephritic glomeruli and mesangial cells // Am. J. Physiol. Renal Physiol. – 1998. – Vol. 274. – P. 473-480.
38. Wang Y., Wang Y.P., Zheng G., Lee V.W., Ouyang L., Chang D.H., Mahajan D., Coombs J., Wang Y.M., Alexander S.I., Harris D.C. Ex vivo programmed macrophages ameliorate experimental chronic inflammatory renal disease // Kidney Int. – 2007. – Vol. 72. – P. 290-299.
39. Yamate J. Heterogeneity of Macrophage populations and myofibroblasts appearing in rat renal interstitial fibrosis // J. Toxicol. Pathol. – 2007. – Vol. 20. – P. 185-195.
40. Yu Zh., Xia X., Kone B.C. Expression profile of a human inducible nitric oxide synthase promoter reporter in transgenic mice during endotoxemia // Am. J. Physiol. Renal Physiol. – 2005. – Vol. 288. – P. 214-220.
41. Zager R.A., Shah V.O., Shah H.V., Zager P.G. Johnson A.C.M., Hanson S. The mevalonate pathway during acute tubular injury. selected determinants and consequences // Am. J. Pathol. – 2002. – Vol. 161. – P. 681-692.
42. Zager R. Rhabdomyolysis and myoglobinuric renal failure // Kidney Int. – 1996. – Vol.49. – P. 314 - 326.
Review
For citations:
Schwarz Ya.Sh., Belogorodtsev S.N., Filimonov P.N., Seledtsova G.V. EFFECTS OF MEVALONATE PATHWAY MODULATORS UPON REACTIVITY OF MACROPHAGES IN E XPERIMENTAL NEPHROSCLEROSIS. Medical Immunology (Russia). 2009;11(6):499-508. (In Russ.) https://doi.org/10.15789/1563-0625-2009-6-499-508
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