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Publication : Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury.

First Author  Aguiar CF Year  2015
Journal  Mol Med Volume  21
Pages  553-62 PubMed ID  26101952
Mgi Jnum  J:313146 Mgi Id  MGI:6791227
Doi  10.2119/molmed.2014.00090 Citation  Aguiar CF, et al. (2015) Administration of alpha-Galactosylceramide Improves Adenine-Induced Renal Injury. Mol Med 21:553-62
abstractText  Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to alpha-galactosylceramide (alphaGalCer). alphaGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-gamma and interleukin (IL)-4. NKT cells and IFN-gamma are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jalpha18KO and IFN-gammaKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jalpha18KO mice exhibited renal dysfunction, but adenine-fed Jalpha18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-alpha and type I collagen. To analyze the role of activated iNKT cells in our model, we administered alphaGalCer in WT mice during adenine ingestion. After alphaGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-gammaKO mice after alphaGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-gamma production is one of the factors contributing to improved renal function after alphaGalCer administration.
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