Endogenous IL-10 attenuates cisplatin nephrotoxicity: role of dendritic cells.
Endogenous IL-10 attenuates cisplatin nephrotoxicity: role of dendritic cells.
复制标题
DOI：
10.4049/jimmunol.1000383
复制
发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Reeves WB
中科院分区：
文献类型：
--
作者：
Tadagavadi RK;Reeves WB
Sterile inflammation is associated with tissue injury and organ failure. Recent studies indicate that certain endogenous cytokines and immune cells may limit tissue injury by reducing immune-mediated inflammatory responses. Cisplatin is a commonly used anticancer chemotherapeutic agent but causes acute kidney injury and dysfunction. In a recent study, we showed that renal dendritic cells attenuate cisplatin-induced kidney injury by reducing inflammation. Here we investigated the effect of endogenous IL-10 and dendritic cell IL-10 in cisplatin-mediated kidney injury. Cisplatin treatment caused increases in renal IL-10R1 expression and STAT3 phosphorylation. In response to cisplatin treatment, IL-10KO mice showed more rapid and greater increases in BUN and serum creatinine compared with WT mice, indicating that endogenous IL-10 ameliorates kidney injury in cisplatin nephrotoxicity. Renal infiltration of IFNγ-producing neutrophils was markedly increased in IL-10KO mice compared with WT mice. However, IFNγ neutralization had no impact on renal dysfunction, suggesting IFNγ independent mechanisms of tissue injury in cisplatin nephrotoxicity. Renal dendritic cells showed high expression of IL-10 in response to cisplatin treatment. We further investigated the effect of dendritic cell-derived IL-10 in cisplatin nephrotoxicity using a conditional cell ablation approach. Mixed bone marrow chimeric mice lacking IL-10 in dendritic cells showed moderately greater renal dysfunction than chimeric mice positive for IL-10 in dendritic cells. These data demonstrate that endogenous IL-10 reduces cisplatin nephrotoxicity and associated inflammation. Moreover, IL-10 produced by dendritic cells themselves accounts for a portion of the protective effect of dendritic cells in cisplatin nephrotoxicity.
登录
查看更多内容
影响因子：
30.5
作者：
Kuwajima, Seiichi;Sato, Taku;Ohteki, Toshiaki
通讯作者：
Ohteki, Toshiaki
影响因子：
4.6
作者：
Kitching, AR;Katerelos, M;Holdsworth, SR
通讯作者：
Holdsworth, SR
影响因子：
19.6
作者：
Goodman, A. I.;Olszanecki, R.;Abraham, N. G.
通讯作者：
Abraham, N. G.
DOI：
10.1126/science.1168988
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen GY;Tang J;Zheng P;Liu Y
通讯作者：
Liu Y
影响因子：
19.6
作者：
Deng, JP;Kohda, Y;Star, RA
通讯作者：
Star, RA