| First Author | Kanbe A | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 490 |
| Issue | 2 | Pages | 364-370 |
| PubMed ID | 28623127 | Mgi Jnum | J:253767 |
| Mgi Id | MGI:6103171 | Doi | 10.1016/j.bbrc.2017.06.049 |
| Citation | Kanbe A, et al. (2017) The inhibition of NLRP3 signaling attenuates liver injury in an alpha-galactosylceramide-induced hepatitis model. Biochem Biophys Res Commun 490(2):364-370 |
| abstractText | 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-1beta-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-alpha) 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-1(int) 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. |
