| Autor: |
Okabe, Cristiene, Borges, Raquel Lerner, de Almeida, Danilo Candido, Fanelli, Camilla, Barlette, Grasiela Pedreira, Machado, Flavia Gomes, Arias, Simone Costa Alarcon, Malheiros, Denise Maria Avancini Costa, Camara, Niels Olsen Saraiva, Zatz, Roberto, Fujihara, Clarice Kazue |
| Zdroj: |
American Journal of Physiology - Renal Physiology; July 2013, Vol. 305 Issue: 2 pF155-F163, 9p |
| Abstrakt: |
Adenine overload promotes intratubular crystal precipitation and interstitial nephritis. We showed recently that these abnormalities are strongly attenuated in mice knockout for Toll-like receptors-2, -4, MyD88, ASC, or caspase-1. We now investigated whether NF-κB activation also plays a pathogenic role in this model. Adult male Munich-Wistar rats were distributed among three groups: C (n= 17), receiving standard chow; ADE (n= 17), given adenine in the chow at 0.7% for 1 wk and 0.5% for 2 wk; and ADE + pyrrolidine dithiocarbamate (PDTC; n= 14), receiving adenine as above and the NF-κB inhibitor PDTC (120 mg·kg−1·day−1in the drinking water). After 3 wk, widespread crystal deposition was seen in tubular lumina and in the renal interstitium, along with granuloma formation, collagen accumulation, intense tubulointerstitial proliferation, and increased interstitial expression of inflammatory mediators. Part of the crystals were segregated from tubular lumina by a newly formed cell layer and, at more advanced stages, appeared to be extruded to the interstitium. p65 nuclear translocation and IKK-α increased abundance indicated activation of the NF-κB system. PDTC treatment prevented p65 migration and normalized IKK-α, limited crystal shift to the interstitium, and strongly attenuated interstitial fibrosis/inflammation. These findings indicate that the complex inflammatory phenomena associated with this model depend, at least in part, on NF-κB activation, and suggest that the NF-κB system may become a therapeutic target in the treatment of chronic kidney disease. |
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