Conjugated linoleic acid reduces inflammation via PPARγ in murine autoimmune glomerulonephritis (THER6P.861)

Abstract

Abstract Conjugated linoleic acid (CLA) has been shown to reduce inflammation via Peroxisome Proliferator-Activated Receptor (PPAR)-γ in inflammatory disorders. We sought to determine whether CLA isomers would reduce inflammation via PPARγ in cultured mesangial cells, and in murine autoimmune glomerulonephritis. Mesangial cells were cultured with pure CLA isomers (c9,t11 or t10,c12) or a 50:50 mixture prior to immune stimulation. Next, cultured mesangial cells were transfected with siRNA targeting PPARγ and treated with CLA isomers prior to immune stimulation. ELISA and RT-qPCR were performed to measure cytokine production and mRNA expression. Treatment with c9,t11 CLA reduced IL-6 production in cultured mesangial cells, but not in siRNA-treated mesangial cells, suggesting c9,t11 CLA acts through PPARγ. IL-1RA mRNA expression was significantly higher in c9,t11-treated siRNA-transfected cells than in t10,c12-treated cells, suggesting alternate pathways in addition to PPARγ. For in vivo studies, wild-type and PPARγ -/- mice were fed a control diet or a CLA-supplemented diet (50:50 mixture of c9,t11 and t10,c12) prior to induction of glomerulonephritis by anti-glomerular basement membrane antisera administration. CLA treatment reduced renal TGFβ in the CLA-treated wildtype mice, but not in the CLA-treated PPARγ-knockout mice. Taken together, these studies suggest that CLA acts in part through PPARγ to decrease inflammatory mediator production in autoimmune glomerulonephritis.