The inhibition of NLRP3 signaling attenuates liver injury in an α-galactosylceramide-induced hepatitis model

Ayumu Kanbe, Hiroyasu Ito, Yukari Omori, Akira Hara, Mitsuru Seishima

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Inflammasomes are involved in innate immune responses. Several NOD-Like receptors (NLRs) participate in the formation of inflammasomes. NACHT, LRR and PYD domains-containing protein 3 (NALP3) belongs to the NLR family and recognizes adenosine triphosphate (ATP), crystals, and Reactive Oxygen Species (ROS). This study examined the effect of inflammasomes on alpha-galactosylceramide (GalCer)-induced liver injury using NALP3-knockout (KO) mice. GalCer administration induced inflammasome activation and IL-1β-maturation. In NALP3-KO mice treated with GalCer, serum ALT levels were significantly reduced compared with those in GalCer-treated WT mice. Histological examination revealed decreased necrosis in NALP3-KO mice compared with WT mice, consistent with ALT levels. Expression of proinflammatory cytokines (such as IL-6, and TNF-α) and chemokines was also significantly suppressed in NALP3-KO mice. Moreover, flow cytometry analysis revealed fewer infiltrating immune cells in the livers of GalCer-treated NALP3-KO mice. Inportantly, the frequency of MDSCs (CD11b+Gr-1int cells), which suppress the immune response, was significantly increased in GalCer-treated NALP3-KO mice. In conclusion, NALP3 inhibition attenuated liver injury in GalCer-induced hepatitis. The inhibition of NALP3 signaling coused be a therapeutic target in immune-mediated liver injury.

Original languageEnglish
Pages (from-to)364-370
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 19-08-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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