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

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Chronic allograft nephropathy (CAN) is a major cause of graft loss following kidney transplantation and may result from the interactions of various immune and nonimmune 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 2,3dioxygenase (IDO), heme oxygenase1 (HO1) and interleukin7 (IL7) in mesangial cells during the healing process as well as to investigate the effects of various immunosuppressants on the expression of these genes. The HBZY1 glomerular mesangial cell line was pretreated in vitro with cytochalasin B for 2 h to induce reversible damage. Following the pretreatment, the HBZY1 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, HO1 and IL7 were examined using reverse transcription quantitative polymerase chain reaction (RTqPCR), western blot and immunohistochemical analyses. The results showed that expression levels of HO1 were significantly upregulated in response to treatment with CsA, FK506, RAPA and MMF, whereas the expression levels of IL7 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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Document Type: Research Article

Affiliations: 1: Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China 2: Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550005, P.R. China 3: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China 4: Transplantation Immunology Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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