Impact of immunosuppressive agents on the expression of indoleamine 2,3-dioxygenase, heme oxygenase-1 and interleukin-7 in mesangial cells

Liang,Guo‑Biao; Luo,Guang‑Heng; Bao,Ding‑Su; Chen,An‑Jian; Zhuang,Yong‑Xiang; Guo,Ya‑Nan; Wang,Xin; Wang,Yuan‑Liang; Chen,Zong‑Ping; Lu,Yi‑Ping; Li,You‑Ping

doi:10.3892/mmr.2015.3713

Impact of immunosuppressive agents on the expression of indoleamine 2,3-dioxygenase, heme oxygenase-1 and interleukin-7 in mesangial cells

Authors:
- Guo‑Biao Liang
- Guang‑Heng Luo
- Ding‑Su Bao
- An‑Jian Chen
- Yong‑Xiang Zhuang
- Ya‑Nan Guo
- Xin Wang
- Yuan‑Liang Wang
- Zong‑Ping Chen
- Yi‑Ping Lu
- You‑Ping Li
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Affiliations: Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China, Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550005, P.R. China, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Transplantation Immunology Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: May 4, 2015 https://doi.org/10.3892/mmr.2015.3713
Pages: 2577-2583
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Chronic allograft nephropathy (CAN) is a major cause of graft loss following kidney transplantation and may result from the interactions of various immune and non‑immune factors. The aim of the present study was to establish an in vitro model of glomerular mesangial cell injury in order to examine the gene expression levels of indoleamine 2,3‑dioxygenase (IDO), heme oxygenase‑1 (HO‑1) and interleukin‑7 (IL‑7) in mesangial cells during the healing process as well as to investigate the effects of various immunosuppressants on the expression of these genes. The HBZY‑1 glomerular mesangial cell line was pre‑treated in vitro with cytochalasin B for 2 h to induce reversible damage. Following the pre‑treatment, the HBZY‑1 cells were divided into five groups: Blank control group, cyclosporine A (CsA) group, tacrolimus (Tac) group, mycophenolate mofetil (MMF) group and rapamycin (RAPA) group. After treating the mesangial cells with each immunosuppressive drug for 6, 12 or 24 h, the mRNA and protein expression levels of IDO, HO‑1 and IL‑7 were examined using reverse transcription quantitative polymerase chain reaction (RT‑qPCR), western blot and immunohistochemical analyses. The results showed that expression levels of HO‑1 were significantly upregulated in response to treatment with CsA, FK506, RAPA and MMF, whereas the expression levels of IL‑7 were markedly downregulated by treatment with the above immunosuppressants. CsA, FK506 and MMF significantly enhanced the expression levels of IDO, whereas RAPA exhibited no apparent effect on IDO. The present study may contribute to the understanding of the pathogenesis of CAN and provide novel strategies for the prevention and treatment of CAN.

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1	Ma X, Lu YP, Yang L, et al: Rapamycin and cyclosporine have different effects on expression of Ang-1 and Ang-2 and Tie2 in rat renal allograft with chronic allograft nephropathy. Transplant Proc. 40:2804–2807. 2008. View Article : Google Scholar : PubMed/NCBI
2	Najafian B and Kasiske BL: Chronic allograft nephropathy. Curr Opin Nephrol Hypertens. 17:149–155. 2008. View Article : Google Scholar : PubMed/NCBI
3	Weissgarten J, Berman S, Efrati S, et al: Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats. Nephrol Dial Transplant. 21:1198–1204. 2006. View Article : Google Scholar : PubMed/NCBI
4	Shultz PJ and Raij L: The glomerular mesangium: Role in initiation and progression of renal injury. Am J Kidney Dis. 17(5 Suppl 1): 8–14. 1991.PubMed/NCBI
5	Chen JK, Zou WZ and You JF: Mesangial cells endothelin receptors. Chinese J Nephrol. 1:52–53. 1997.In Chinese.
6	Joosten SA, van Kooten C and Paul LC: Pathogenesis of chronic allograft rejection. Transpl Int. 16:137–145. 2003. View Article : Google Scholar : PubMed/NCBI
7	Libby P and Pober JS: Chronic rejection. Immunity. 14:387–397. 2001. View Article : Google Scholar : PubMed/NCBI
8	Joosten SA, van Ham V, Borrias MC, et al: Antibodies against mesangial cells in a rat model of chronic renal allograft rejection. Nephrol Dial Transplant. 20:692–698. 2005. View Article : Google Scholar : PubMed/NCBI
9	Hill M, Zagani R, Voisine C, et al: Nitric oxide and indoleamine 2,3-dioxygenase mediate CTLA4Ig-induced survival in heart allografts in rats. Transplantation. 84:1060–1063. 2007. View Article : Google Scholar : PubMed/NCBI
10	Brandacher G, Margreiter R and Fuchs D: Clinical relevance of indoleamine 2,3-dioxygenase for alloimmunity and transplantation. Curr Opin Organ Transplant. 13:10–15. 2008. View Article : Google Scholar : PubMed/NCBI
11	Vogel CF, Goth SR, Dong B, et al: Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun. 375:331–335. 2008. View Article : Google Scholar : PubMed/NCBI
12	Dai H and Dai Z: The role of tryptophan catabolism in acquisition and effector function of memory T cells. Curr Opin Organ Transplant. 13:31–35. 2008. View Article : Google Scholar : PubMed/NCBI
13	Arefayene M, Philips S, Cao D, et al: Identification of genetic variants in the human indoleamine 2,3-dioxygenase (IDO1) gene, which have altered enzyme activity. Pharmacogenet Genomics. 19:464–476. 2009. View Article : Google Scholar : PubMed/NCBI
14	Lai IR, Chang KJ, Tsai HW and Chen CF: Pharmacological preconditioning with simvastatin protects liver from ischemia-reperfusion injury by heme oxygenase-1 induction. Transplantation. 85:732–738. 2008. View Article : Google Scholar : PubMed/NCBI
15	Chen C, Wang Y, Zhang Z, et al: Toll-like receptor 4 regulates heme oxygenase-1 expression after hemorrhagic shock induced acute lung injury in mice: Requirement of p38 mitogen-activated protein kinase activation. Shock. 31:486–492. 2009. View Article : Google Scholar
16	Lin CC, Liu XM, Peyton K, et al: Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1. Arterioscler Thromb Vasc Biol. 28:739–745. 2008. View Article : Google Scholar : PubMed/NCBI
17	Saleem S, Zhuang H, Biswal S, et al: Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke. 39:3389–3396. 2008. View Article : Google Scholar : PubMed/NCBI
18	Krönke G, Kadl A, Ikonomu E, et al: Expression of heme oxygenase-1 in human vascular cells is regulated by peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 27:1276–1282. 2007. View Article : Google Scholar
19	Tiroch K, Koch W, von Beckerath N, et al: Heme oxygenase-1 gene promoter polymorphism and restenosis following coronary stenting. Eur Heart J. 28:968–973. 2007. View Article : Google Scholar : PubMed/NCBI
20	Lang D, Reuter S, Buzescu T, et al: Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation. Int Immunol. 17:155–165. 2005. View Article : Google Scholar
21	Dulak J, Loboda A and Jozkowicz A: Effect of heme oxygenase-1 on vascular function and disease. Curr Opin Lipidol. 19:505–512. 2008. View Article : Google Scholar : PubMed/NCBI
22	Dulak J, Deshane J, Jozkowicz A and Agarwal A: Heme oxygenase-1 and carbon monoxide in vascular pathobiology: Focus on angiogenesis. Circulation. 117:231–241. 2008. View Article : Google Scholar : PubMed/NCBI
23	Ryter SW, Alam J and Choi AM: Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications. Physiol Rev. 86:583–650. 2006. View Article : Google Scholar : PubMed/NCBI
24	Nginamau ES, Maehle BO and Jonsson R: An experimental protocol for the fractionation and 2DE separation of HeLa and A-253 cell lysates suitable for the identification of the individual antigenic proteome in Sjögren’s syndrome. Autoimmunity. 44:652–663. 2011. View Article : Google Scholar : PubMed/NCBI
25	Radu CA, Bosch N, Bauer TM, et al: Immunosuppressive effect of tryptophan metabolites in composite tissue allotransplantation. Plast Reconstr Surg. 119:2023–2028. 2007. View Article : Google Scholar : PubMed/NCBI
26	Niederkorn JY: Emerging concepts in CD8(+) T regulatory cells. Curr Opin Immunol. 20:327–331. 2008. View Article : Google Scholar : PubMed/NCBI
27	Nath KA: Heme oxygenase-1: A provenance for cytoprotective pathways in the kidney and other tissues. Kidney Int. 70:432–443. 2006.PubMed/NCBI
28	Kassovska-Bratinova S, Yang G, Igarashi K and Dennery PA: Bach1 modulates heme oxygenase-1 expression in the neonatal mouse lung. Pediatr Res. 65:145–149. 2009. View Article : Google Scholar :
29	von Dobschuetz E, Schmidt R, Scholtes M, et al: Protective role of heme oxygenase-1 in pancreatic microcirculatory dysfunction after ischemia/reperfusion in rats. Pancreas. 36:377–384. 2008. View Article : Google Scholar : PubMed/NCBI
30	Di Francesco L, Totani L, Dovizio M, et al: Induction of prostacyclin by steady laminar shear stress suppresses tumor necrosis factor-alpha biosynthesis via heme oxygenase-1 in human endothelial cells. Circ Res. 104:506–513. 2009. View Article : Google Scholar : PubMed/NCBI
31	Abraham NG and Kappas A: Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev. 60:79–127. 2008. View Article : Google Scholar : PubMed/NCBI
32	Roach JP, Moore EE, Partrick DA, et al: Heme oxygenase-1 induction in macrophages by a hemoglobin-based oxygen carrier reduces endotoxin-stimulated cytokine secretion. Shock. 31:251–257. 2009. View Article : Google Scholar
33	Kaczorowski DJ, Nakao A, Mollen KP, et al: Toll-like receptor 4 mediates the early inflammatory response after cold ischemia/reperfusion. Transplantation. 84:1279–1287. 2007. View Article : Google Scholar : PubMed/NCBI
34	Rethi B, Vivar N, Sammicheli S and Chiodi F: Limited efficiency of endogenous interleukin-7 levels in T cell reconstitution during HIV-1 infection: Will exogenous interleukin-7 therapy work-AIDS. 23:745–755. 2009.
35	Song J, Lu YP, Luo GH, et al: Effects of mycophenolate mofetil on chronic allograft nephropathy by affecting RHO/ROCK signal pathways. Transplant Proc. 40:2790–2794. 2008. View Article : Google Scholar : PubMed/NCBI
36	Siemionow M and Klimczak A: Basics of immune responses in transplantation in preparation for application of composite tissue allografts in plastic and reconstructive surgery: Part 1. Plast Reconstr Surg. 121:4e–12e. 2008. View Article : Google Scholar
37	Tanabe K: Japanese experience of ABO-incompatible living kidney transplantation. Transplantation. 84(12 Suppl): S4–S7. 2007. View Article : Google Scholar
38	Monti P, Scirpoli M, Maffi P, et al: Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells. J Clin Invest. 118:1806–1814. 2008.PubMed/NCBI
39	Donckier V, Craciun L, Lucidi V, et al: Acute liver transplant rejection upon immunosuppression withdrawal in a tolerance induction trial: Potential role of IFN-gamma-secreting CD8+ T cells. Transplantation. 87(9 Suppl): S91–S95. 2009. View Article : Google Scholar : PubMed/NCBI
40	Daudt L, Maccario R, Locatelli F, et al: Interleukin-15 favors the expansion of central memory CD8+ T cells in ex vivogenerated, antileukemia human cytotoxic T lymphocyte lines. J Immunother. 31:385–393. 2008. View Article : Google Scholar : PubMed/NCBI