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免疫抑制剂对系膜细胞中吲哚胺2,3-双加氧酶、血红素加氧酶-1和白细胞介素-7表达的影响。

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

作者信息

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

机构信息

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.

出版信息

Mol Med Rep. 2015 Aug;12(2):2577-83. doi: 10.3892/mmr.2015.3713. Epub 2015 May 4.

DOI:10.3892/mmr.2015.3713
PMID:25936769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4464319/
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.

摘要

慢性移植肾肾病（CAN）是肾移植后移植物丢失的主要原因，可能由多种免疫和非免疫因素相互作用引起。本研究的目的是建立肾小球系膜细胞损伤的体外模型，以检测愈合过程中系膜细胞中吲哚胺2,3-双加氧酶（IDO）、血红素加氧酶-1（HO-1）和白细胞介素-7（IL-7）的基因表达水平，并研究各种免疫抑制剂对这些基因表达的影响。将HBZY-1肾小球系膜细胞系在体外先用细胞松弛素B预处理2小时以诱导可逆性损伤。预处理后，将HBZY-1细胞分为五组：空白对照组、环孢素A（CsA）组、他克莫司（Tac）组、霉酚酸酯（MMF）组和雷帕霉素（RAPA）组。用每种免疫抑制药物处理系膜细胞6、12或24小时后，使用逆转录定量聚合酶链反应（RT-qPCR）、蛋白质印迹和免疫组织化学分析检测IDO、HO-1和IL-7的mRNA和蛋白质表达水平。结果显示，HO-1的表达水平在CsA、FK506、RAPA和MMF处理后显著上调，而上述免疫抑制剂处理后IL-7的表达水平明显下调。CsA、FK506和MMF显著提高了IDO的表达水平，而RAPA对IDO没有明显影响。本研究可能有助于理解CAN的发病机制，并为CAN的预防和治疗提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/ca431c807533/MMR-12-02-2577-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/f518a998db8a/MMR-12-02-2577-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/eb0bf2fd1d4a/MMR-12-02-2577-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/ea7cd9ebfdcb/MMR-12-02-2577-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/d534551ef5f2/MMR-12-02-2577-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/ca431c807533/MMR-12-02-2577-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/f518a998db8a/MMR-12-02-2577-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/eb0bf2fd1d4a/MMR-12-02-2577-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/ea7cd9ebfdcb/MMR-12-02-2577-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/d534551ef5f2/MMR-12-02-2577-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbf/4464319/ca431c807533/MMR-12-02-2577-g04.jpg

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