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Cited by 866

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TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity

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Ganesan Ramesh, William Brian Reeves·2002·Journal of Clinical Investigation
DOI 10.1172/jci15606
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Abstract

The purpose of these studies was to examine the role of cytokines in the pathogenesis of cisplatin nephrotoxicity. Injection of mice with cisplatin (20 mg/kg) led to severe renal failure. The expression of cytokines, chemokines, and ICAM-1 in kidney was measured by ribonuclease protection assays and RT-PCR. We found significant upregulation of TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1, TCA3, IL-1beta, and ICAM-1 in kidneys from cisplatin-treated animals. In addition, serum, kidney, and urine levels of TNF-alpha measured by ELISA were increased by cisplatin. Inhibitors of TNF-alpha production (GM6001, pentoxifylline) and TNF-alpha Ab's reduced serum and kidney TNF-alpha protein levels and also blunted the cisplatin-induced increases in TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1, and IL-1beta, but not ICAM-1, mRNA. In addition, the TNF-alpha inhibitors also ameliorated cisplatin-induced renal dysfunction and reduced cisplatin-induced structural damage. Likewise, TNF-alpha-deficient mice were resistant to cisplatin nephrotoxicity. These results indicate cisplatin nephrotoxicity is characterized by activation of proinflammatory cytokines and chemokines. TNF-alpha appears to play a central role in the activation of this cytokine response and also in the pathogenesis of cisplatin renal injury.

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Metadata

Authors
Ramesh, G., & Reeves, W. B.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2002-09-15
Volume
110
Issue
6
Pages
835-842
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci15606
OpenAlex
W2021131539
Cited by
866
References
1
FWCI
10.13
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. https://app.cochat.ai/papers/10.1172/jci15606
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Ramesh, G., & Reeves, W. B. (2002). TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. Journal of Clinical Investigation. https://doi.org/10.1172/jci15606

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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