Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury.

Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1β compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI.
AuthorsTakanori Komada, Fumitake Usui, Akira Kawashima, Hiroaki Kimura, Tadayoshi Karasawa, Yoshiyuki Inoue, Motoi Kobayashi, Yoshiko Mizushina, Tadashi Kasahara, Shun'ichiro Taniguchi, Shigeaki Muto, Daisuke Nagata, Masafumi Takahashi
JournalScientific reports (Sci Rep) Vol. 5 Pg. 10901 ( 2015) ISSN: 2045-2322 [Electronic] England
PMID26045078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

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