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Interleukin-1? and Interleukin-1? play a central role in the pathogenesis of fulminant hepatic failure in mice.

ABSTRACT: 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)-1? and IL-1? 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-1? and IL-1? in the progression of LPS/GalN-induced FHF.WT, IL-1? or IL-1? deficient mice were injected with LPS/GalN. Blood and liver tissue were collected at different time points, FHF related pathways were examined.After FHF induction the survival of both IL-1? and IL-1? KO mice was longer than that of WT mice. Lower serum liver enzyme levels, demonstrated reduced hepatic injury in the IL-1? and IL-1?KO mice. Histologically detected liver injury and apoptotic hepatocytes were significantly reduced in the IL-1?and IL-1?KO mice compared to WT mice. Reduced hepatic IkB levels and upregulated NF?B activity in WT mice remained inhibited in IL-1? and IL-1? KO mice. Hepatic expression levels of TNF? and IL-6 were significantly increased in WT mice but not in IL-1? and IL-1? KO mice.IL-1? and IL-1? play a central role in the pathogenesis of LPS/GalN-induced FHF. These interleukins are associated with the activation of NF?B signaling, upregulation of the pro-inflammatory cytokines and liver damage and apoptosis. Since neither IL-1? nor IL-1? depletions completely rescued the phenotype, we believe that IL-1? and IL-1? have a similar and probably complementary role in FHF progression.

SUBMITTER: Sultan M

PROVIDER: S-EPMC5617151 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice.

Sultan Maya M Ben-Ari Ziv Z Masoud Rula R Pappo Orit O Harats Dror D Kamari Yehuda Y Safran Michal M

PloS one 20170927 9

<h4>Background and aims</h4>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-1β 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-1β in the progression of LPS/GalN-induced FHF.<h4>Methods</h4>WT, IL-1α or IL-1β deficient mice were injec ...[more]

PMID: 28953903

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Project description:Fulminant hepatic failure (FHF) is defined as rapid acute liver injury, often complicated with spontaneous bacterial peritonitis (SBP). The precise onset of FHF with SBP is still unknown, but it is thought that SBP closely correlates with a weakened intestinal barrier. Dendritic cells (DCs) play a crucial role in forming the intestinal immune barrier, therefore the number, maturity and chemotactic ability of intestinal DCs were studied in FHF. Mouse intestinal and spleen DCs were isolated by magnetic-activated cell sorting (MACS) and surface markers of DCs, namely CD11c, CD74, CD83 and CD86, were identified using flow cytometry. Immunohistochemistry and Western blotting were performed to detect the distribution and expression of CC-chemokine receptor 7 (CCR7) and CC-chemokine receptor 9 (CCR9), as well as their ligands-CC-chemokine ligand 21 (CCL21) and CC-chemokine ligand 25 (CCL25). Real-time PCR was used to detect CCR7 and CCR9 mRNA, along with their ligands-CCL21 and CCL25 mRNA. Flow cytometry analysis showed that the markers CD74, CD83 and CD86 of CD11c+DCs were lower in the D-galactosamine (D-GalN) group and were significantly decreased in the FHF group, while there were no significant changes in the expression of these markers in the lipopolysaccharide (LPS) group. Immunohistochemistry results showed that staining for CCR7 and CCR9, as well as their ligands CCL21 and CCL25, was significantly weaker in the D-GalN and FHF groups compared with the normal saline (NS) group or the LPS group; the FHF group even showed completely unstained parts. Protein expression of CCR7 and CCR9, as well as their ligands- CCL21 and CCL25, was also lower in the D-GalN group and decreased even more significantly in the FHF group. At the gene level, CCR7 and CCR9, along with CCL21 and CCL25 mRNA expression, was lower in the D-GalN group and significantly decreased in the FHF group compared to the NS and LPS groups, consisting with the protein expression. Our study indicated that intestinal DCs were decreased in number, maturity and chemotactic ability in FHF and might contribute to a decreased function of the intestinal immune barrier in FHF.

Dataset Information

Interleukin-1? and Interleukin-1? play a central role in the pathogenesis of fulminant hepatic failure in mice.

Publications

Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice.

Similar Datasets

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