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Cytokine Array After Cyclosporine Treatment in Rats

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Author(s)
K.B. JinH.J. ChoiH.T. KimE.A. HwangS.Y. HanS.B. ParkH.C. KimE.Y. HaY.H. KimS.I. SuhK.C. Mun
Keimyung Author(s)
Ha, Eun YoungMun, Kyo CheolKim, You HeeJin, Kyu BokHwang, Eun AhHan, Seung YeupPark, Sung BaeKim, Hyun ChulKim, Hyoung TaeSuh, Seong Il
Department
Dept. of Biochemistry (생화학)
Dept. of Internal Medicine (내과학)
Dept. of Surgery (외과학)
Dept. of Microbiology (미생물학)
Kidney Institute (신장연구소)
Journal Title
Transplantation proceedings
Issued Date
2008
Volume
40
Issue
8
Abstract
Objectives
Long-term treatment with cyclosporine (CsA) results in chronic nephrotoxicity, which is known to be mediated by several cytokines including transforming growth factor-betal. Cytokines are known to play an important role in innate immunity, apoptosis, angiogenesis, cell growth, and differentiation. They are known to be involved in most disease processes, including cancer, cardiac disease, and nephrotoxicity. To evaluate changes of cytokines in a rat model of CsA-induced chronic nephrotoxicity, we performed a cytokine array.

Methods

Experiments were performed on two groups of rats; normal control group and CsA-treated group. Cytokine array in rat serum was performed using Cytokine Antibody Array I kit from RayBiotech.

Results

Serum creatinine, urine creatinine, and creatinine clearance increased in the CsA-treated group. Among the several cytokines, the expressions of the lipopolysaccharide-induced CXC chemokine (LIX), monocyte chemoattractant protein 1 (MCP-1), nerve growth factor (β-NGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the CsA-treated group were increased above that of cytokines in the control group. The density of the LIX in controls was 0.62, and in the CsA-treated group was 1.24. The density of the MCP-1 in controls was 0.68, and in CsA-treated, 1.43. The density of the β-NGF in controls was 0.62, and that in CsA-treated, 1.24. The density of the TIMP-1 in controls 1.13, and in CsA-treated, 1.40.

Conclusions

Our data suggested that among several cytokines elevated levels of the LIX, MCP-1, β-NGF, and TIMP-1 are the contributing factors to CsA-induced nephropathy.



Nephrotoxicity, characterized by functional and morphological changes,1 is the most clinically important side effect of cyclosporine (CsA).2, 3 and 4 The pathogenesis of CsA-induced nephrotoxicity has been known to be secondary to hemodynamic changes, but increasing evidence indicates that CsA has a direct toxicity on renal tubular cells, leading to apoptosis and tubulointerstitial fibrosis.5 According to Lee et al,5 CsA induces tubular cell apoptosis, cellular infiltration, and increased cytokine expression, producing significant tubulointerstitial fibrosis. According to several reports,5, 6 and 7 CsA induces interstitial fibrosis and stimulates cytokine release by tubular cells, thus inducing nephropathy via tubulointerstitial injury. In this study, we evaluated change in cytokines within a rat model of CsA-induced chronic nephrotoxicity using cytokine array.
Keimyung Author(s)(Kor)
하은영
문교철
김여희
진규복
황은아
한승엽
박성배
김현철
김형태
서성일
Publisher
School of Medicine
Citation
K.B. Jin et al. (2008). Cytokine Array After Cyclosporine Treatment in Rats. Transplantation proceedings, 40(8), 2682–2684. doi: 10.1016/j.transproceed.2008.08.008
Type
Article
ISSN
0041-1345
Source
https://www.sciencedirect.com/science/article/pii/S0041134508010580?via%3Dihub
DOI
10.1016/j.transproceed.2008.08.008
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34735
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
3. Research Institutues (연구소) > Kidney Institute (신장연구소)
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