Antroquinonol differentially modulates T cell activity and reduces interleukin-18 production, but enhances Nrf2 activation, in murine accelerated severe lupus nephritis.

摘要: Objective Accelerated severe lupus nephritis (ASLN), with an acute onset of clinical manifestations and histopathologic renal lesions, may represent transformation mild LN to a form glomerulonephritis. Abnormal activation T B cells and/or oxidative stress play major role in the pathogenesis ASLN. This study tested hypothesis that antroquinonol, purified compound effective component Antrodia camphorata antiinflammatory antioxidant activities, might prevent into higher-grade (severe) murine model. Methods Experimental ASLN was induced (NZB × NZW)F1 mice by twice weekly intraperitoneal injections Salmonella-type lipopolysaccharide (LPS). Starting 2 days after first dose LPS, were treated daily administered gavage, for different durations up 5 weeks. Results Antroquinonol administration significantly ameliorated proteinuria, hematuria, impairment function, development especially cellular crescent formation, neutrophil infiltration, fibrinoid necrosis, cell proliferation glomerulus, as well periglomerular interstitial inflammation. Mechanistic analyses revealed antroquinonol 1) inhibited activation/proliferation, but enhanced Treg suppression reduced production interleukin-18 (IL-18); 2) reactive oxygen species nitric oxide, increased Nrf2 kidney; 3) suppressed inflammation via blocking NF-κB activation. Conclusion Antroquinonol have therapeutic potential early treatment its differential regulation function lowering IL-18 production, also promotion activation.