Interleukin-1α and Interleukin-1ß play a central role in the pathogenesis of fulminant hepatic failure in mice.
PLoS One
; 12(9): e0184084, 2017.
Article
em En
| MEDLINE
| ID: mdl-28953903
ABSTRACT
BACKGROUND AND AIMS:
Fulminant hepatitis failure (FHF) is marked by the sudden loss of hepatic function, with a severe life-threatening course in persons with no prior history of liver disease. Interleukin (IL)-1α and IL-1ß are key inflammatory cytokines but little is known about their role in the development of FHF. The aim of this study was to assess the involvement of IL-1α and IL-1ß in the progression of LPS/GalN-induced FHF.METHODS:
WT, IL-1α or IL-1ß deficient mice were injected with LPS/GalN. Blood and liver tissue were collected at different time points, FHF related pathways were examined.RESULTS:
After FHF induction the survival of both IL-1α and IL-1ß KO mice was longer than that of WT mice. Lower serum liver enzyme levels, demonstrated reduced hepatic injury in the IL-1α and IL-1ßKO mice. Histologically detected liver injury and apoptotic hepatocytes were significantly reduced in the IL-1αand IL-1ßKO mice compared to WT mice. Reduced hepatic IkB levels and upregulated NFκB activity in WT mice remained inhibited in IL-1α and IL-1ß KO mice. Hepatic expression levels of TNFα and IL-6 were significantly increased in WT mice but not in IL-1α and IL-1ß KO mice.CONCLUSIONS:
IL-1α and IL-1ß play a central role in the pathogenesis of LPS/GalN-induced FHF. These interleukins are associated with the activation of NFκB signaling, upregulation of the pro-inflammatory cytokines and liver damage and apoptosis. Since neither IL-1α nor IL-1ß depletions completely rescued the phenotype, we believe that IL-1α and IL-1ß have a similar and probably complementary role in FHF progression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Falência Hepática Aguda
/
Interleucina-1alfa
/
Interleucina-1beta
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article