Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

Abstract

Xenon, an inert anesthetic gas, is increasingly recognized to possess desirable properties including cytoprotective and anti-inflammatory effects. Here we evaluated the effects of xenon on the progression of lupus nephritis (LN) in a mouse model. A two hour exposure of either 70% xenon or 70% nitrogen balanced with oxygen was administered daily for five weeks to female NZB/W F1 mice that had been induced to develop accelerated and severe LN. Xenon treatment improved kidney function and renal histology, and decreased the renal expression of neutrophil chemoattractants, thereby attenuating glomerular neutrophil infiltration. The effects of xenon were mediated primarily by deceasing serum levels of anti-double stranded DNA autoantibody, inhibiting reactive oxygen species production, NF-κB/NLRP3 inflammasome activation, ICAM-1 expression, glomerular deposition of IgG and C3 and apoptosis, in the kidney; and enhancing renal hypoxia inducible factor 1-α expression. Proteomic analysis revealed that the treatment with xenon downregulated renal NLRP3 inflammasome-mediated cellular signaling. Similarly, xenon was effective in improving renal pathology and function in a spontaneous LN model in female NZB/W F1 mice. Thus, xenon may have a therapeutic role in treating LN but further studies are warranted to determine applicability to patients.