Impact of immunosuppressive agents on the expression of indoleamine 2,3-dioxygenase, heme oxygenase-1 and interleukin-7 in mesangial cells.
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.
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Guo-Biao
GB
Liang
Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550005, P.R. China.
Guang-Heng
GH
Luo
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Ding-Su
DS
Bao
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
An-Jian
AJ
Chen
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Yong-Xiang
YX
Zhuang
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Ya-Nan
YN
Guo
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Xin
X
Wang
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Yuan-Liang
YL
Wang
Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Zong-Ping
ZP
Chen
Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Yi-Ping
YP
Lu
Transplantation Immunology Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
You-Ping
YP
Li
D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
C576710:IDO1 protein, human; C508605:IL7 protein, human; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015851:Interleukin-7; D012333:RNA, Messenger; D003571:Cytochalasin B; D016572:Cyclosporine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus