| First Author | Tadagavadi RK | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 8 | Pages | 4904-11 |
| PubMed ID | 20844196 | Mgi Jnum | J:219402 |
| Mgi Id | MGI:5620600 | Doi | 10.4049/jimmunol.1000383 |
| Citation | Tadagavadi RK, et al. (2010) Endogenous IL-10 attenuates cisplatin nephrotoxicity: role of dendritic cells. J Immunol 185(8):4904-11 |
| abstractText | 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. In this study, 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-10 knockout mice showed more rapid and greater increases in blood urea nitrogen and serum creatinine compared with wild-type mice, indicating that endogenous IL-10 ameliorates kidney injury in cisplatin nephrotoxicity. Renal infiltration of IFN-gamma-producing neutrophils was markedly increased in IL-10 knockout mice compared with wild-type mice. However, IFN-gamma neutralization had no impact on renal dysfunction, suggesting IFN-gamma-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. |
