Characterization and Activation of NLRP3 Inflammasomes in the Renal Medulla in Mice

• Published in: Kidney & blood pressure research Vol. 41; no. 2; pp. 208 - 221
• Main Authors: Xia, Min, Abais, Justine M., Koka, Saisudha, Meng, Nan, Gehr, Todd W., Boini, Krishna M., Li, Pin-Lan
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-03-2016; Karger Publishers
• Subjects: Alzheimer's disease; Animals; Blood flow; Blood Flow Velocity; Blood pressure; Caspase-1; Catheters; Cellular inflammation; Confocal microscopy; Dissection; Excretion; Gene Deletion; Hemodynamics; Immunohistochemistry; Inflammasomes; Inflammasomes - genetics; Inflammasomes - metabolism; Inflammation; Inflammatory mediators; Inflammatory response; Kidney diseases; Kidney Medulla - blood supply; Kidney Medulla - metabolism; Kidney Medulla - pathology; Kidneys; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original Paper; Ostomy; Regulatory mechanisms (biology); Renal function; Renal medulla; Rheumatism; Sodium; Uric acid; Urinary excretion; Cellular inflammation; Renal medulla; Uric acid; Inflammatory mediators; Urinary excretion
• ISSN: 1420-4096; 1423-0143
• DOI: 10.1159/000443424

Abstract
Background/Aims: Recent studies have indicated that local inflammatory mediators are importantly involved in the regulation of renal function. However, it remains unknown how such local inflammation is triggered intracellularly in the kidney. The present study was designed to characterize the inflammasome centered by Nlrp3 in the kidney and also test the effect of its activation in the renal medulla. Methods and Results: By immunohistochemistry analysis, we found that inflammasome components, Nlrp3, Asc and caspase-1, were ubiquitously distributed in different kidney areas. The caspase-1 activity and IL-1β production were particularly high in the renal outer medulla compared to other kidney regions. Further confocal microscopy and RT-PCR analysis showed that Nlrp3, Asc and caspase-1 were particularly enriched in the thick ascending limb of Henle's loop. In anesthetized mice, medullary infusion of Nlrp3 inflammasome activator, monosodium urate (MSU), induced significant decreases in sodium excretion and medullary blood flow without changes in mean arterial blood pressure and renal cortical blood flow. Caspase-1 inhibitor, Ac-YVAD-CMK and deletion of Nlrp3 or Asc gene abolished MSU-induced decreases in renal sodium excretion and MBF. Conclusion: Our results indicate that renal medullary Nlrp3 inflammasomes represent a new regulatory mechanism of renal MBF and sodium excretion which may not depend on classical inflammatory response.