NKT cell modulates NAFLD potentiation of metabolic oxidative stress-induced mesangial cell activation and proximal tubular toxicity.

NKT cell modulates NAFLD potentiation of metabolic oxidative stress-induced mesangial cell activation and proximal tubular toxicity. Am J Physiol Renal Physiol. 2015 Oct 7;:ajprenal.00243.2015 Authors: Alhasson F, Dattaroy D, Das S, Chandrashekaran V, Seth RK, Schnellmann RG, Chatterjee S Abstract Obesity and nonalcoholic fatty liver disease (NAFLD) are associated with the development and progression of chronic kidney disease. We recently showed that NAFLD induces liver specific CYP2E1-mediated metabolic oxidative stress following administration of a CYP2E1 substrate bromodichloromethane (BDCM). The present study examined the effects of CYP2E1 mediated oxidative stress in NAFLD leading to kidney toxicity. Mice were fed a high fat diet for 12 weeks to induce NAFLD. NAFLD mice were exposed to BDCM, a CYP2E1 substrate for 4 weeks. NAFLD+BDCM increased CYP2E1-mediated lipid peroxidation in proximal tubular cells compared to mice with NAFLD alone or BDCM -treated lean mice thus ruling out the exclusive role of BDCM. The lipid peroxidation increased IL1β, TNFα and IFN-γ. In parallel mesangial cell activation was observed by increased α-SMA and TGF-β, which was blocked by the CYP2E1 inhibitor Diallyl sulphide (DAS) both in vivo and in vitro Mice lacking NKT cells (CD1d KO) showed elevated (>4-fold) pro-inflammatory mediator release, increased TLR4 and PDGF2 mRNA and mesangial cell activation in the kidney. Finally, NAFLD-CD1D KO mic...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research