Characterization and activation of NLRP3 inflammasomes in the renal medulla in mice

Min Xia, Justine M. Abais, Saisudha Koka, Nan Meng, Todd W. Gehr, Krishna M. Boini, Pin Lan Li

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)208-221
Number of pages14
JournalKidney and Blood Pressure Research
Volume41
Issue number2
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Inflammasomes
Kidney
Caspase 1
Sodium
Uric Acid
Arterial Pressure
Loop of Henle
Renal Circulation
Interleukin-1
Confocal Microscopy
Immunohistochemistry
Inflammation
Polymerase Chain Reaction

Keywords

  • Cellular inflammation
  • Inflammatory mediators
  • Renal medulla
  • Uric acid
  • Urinary excretion

ASJC Scopus subject areas

  • Nephrology
  • Cardiology and Cardiovascular Medicine

Cite this

Xia, M., Abais, J. M., Koka, S., Meng, N., Gehr, T. W., Boini, K. M., & Li, P. L. (2016). Characterization and activation of NLRP3 inflammasomes in the renal medulla in mice. Kidney and Blood Pressure Research, 41(2), 208-221. https://doi.org/10.1159/000443424

Characterization and activation of NLRP3 inflammasomes in the renal medulla in mice. / Xia, Min; Abais, Justine M.; Koka, Saisudha; Meng, Nan; Gehr, Todd W.; Boini, Krishna M.; Li, Pin Lan.

In: Kidney and Blood Pressure Research, Vol. 41, No. 2, 01.03.2016, p. 208-221.

Research output: Contribution to journalArticle

Xia, M, Abais, JM, Koka, S, Meng, N, Gehr, TW, Boini, KM & Li, PL 2016, 'Characterization and activation of NLRP3 inflammasomes in the renal medulla in mice', Kidney and Blood Pressure Research, vol. 41, no. 2, pp. 208-221. https://doi.org/10.1159/000443424
Xia, Min ; Abais, Justine M. ; Koka, Saisudha ; Meng, Nan ; Gehr, Todd W. ; Boini, Krishna M. ; Li, Pin Lan. / Characterization and activation of NLRP3 inflammasomes in the renal medulla in mice. In: Kidney and Blood Pressure Research. 2016 ; Vol. 41, No. 2. pp. 208-221.
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