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Abstract: FR-PO852

Xenon Blunts NF-κB/NLRP3 Inflammasome Activation and Improves Acute Onset of Accelerated and Severe Lupus Nephritis in Mice

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Ka, Shuk-Man, National Defense Medical Center, Taipei, Taiwan, Taipei, Taiwan
  • Chen, Ann, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taipei, Taiwan
Background

Accelerated and severe lupus nephritis (LN) might follow episodes of bacterial or viral infections as environmental triggers in patients with LN. Xenon (Xe), an anesthetic gas, is increasingly recognized to possess many desirable properties, including cytoprotective and anti-inflammatory effects.

Methods

The present study evaluated the effects of Xe on the progression of LN in a mouse model. A mixture of either 70% Xe or 70% N2 balanced with O2 was given daily to female NZB/W F1 mice with acute onset of progressive renal lesions and renal functional disturbance for 2 hrs for 5 weeks. Renal function and pathology and mechanistic studies were performed, including reactive oxygen species (ROS) production, activation of NF-κB/NLRP3 inflammasome and apoptosis-related pathway, proteomics-based NLRP3 inflammasome-mediated signaling.

Results

The mice that were induced of accelerated and severe LN were successfully treated with Xe in renal function and pathology, chemoattractants for neutrophils, and glomerular neutrophil infiltration, primarily through inhibiting ROS production, NF-κB/NLRP3 inflammasome activation, ICAM-1 expression, and apoptosis in the kidney. Moreover, Xe reduced the expression of p-NF-κB p65, ICAM-1 and p-p38 MAPK, and inhibited levels of total and mitochondrial ROS production as well as mitochondrial damage in activated primary mesangial cells. Proteomics analysis revealed that the Xe treatment downregulated renal NLRP3 inflammasome-mediated cellular signaling.

Conclusion

The results suggest that Xe may shed light of therapeutic value in treating such cases of LN although it might warrant further study.

Funding

  • Government Support - Non-U.S.