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Caspase-1 aggravates the D-galactosamine/lipopolysaccharide induced acute liver failure in mice through activating glycogen synthase kinase-3β / 中华微生物学和免疫学杂志
Chinese Journal of Microbiology and Immunology ; (12): 132-137, 2016.
Article in Chinese | WPRIM | ID: wpr-487575
ABSTRACT
Objective To analyze the role of cysteinyl aspartate specific proteinase-1 (caspase-1) in a mouse model of D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced acute liver failure (ALF) and to study the possible mechanism. Methods C57BL/ 6 mice were randomly divided into four groups including control group, Z-WEHD-FMK (caspase-1 inhibitor) treatment group, ALF model group and Z-WEHD-FMK-treated ALF group. The mouse model of ALF was established by intraperitoneally injec-ting the mice with D-GalN (450 mg/ kg) and LPS (10 μg/ kg). The damages in liver tissues were evaluated based on the histopathological examination and the levels of alanine transaminase (ALT) and aspartate trans-aminase (AST) in serum samples. Western blot assay was performed to analyze the expression of caspase-1 and the phosphorylation of glycogen synthase kinase 3β (GSK-3β). The qRT-PCR was used to measure the expression of inflammatory cytokines at transcriptional level. Results The expression of caspase-1 at both mRNA and protein levels were gradually increased during the development of ALF. Compared with the mice with ALF, those in the Z-WEHD-FMK-treated ALF group showed less severe liver damages on histopatholog-ical examination and decreased levels of ALT and AST in serum samples [ALT (479. 2±39. 5) U/ L vs (998. 5±60. 4 ) U/ L, P<0. 05; AST ( 478. 5±28. 6) U/ L vs ( 1 180. 7±91. 4) U/ L, P<0. 05]. The expression of TNF-α, IL-1β, IL-18 and IL-33 at transcriptional level were significantly suppressed in mice with ALF upon the Z-WEHD-FMK intervention. Results of the Western blot assay indicated that Z-WEHD-FMK suppressed the activities of GSK-3β by enhancing its phosphorylation. Conclusion This study demon-strated that caspase-1 could promote the activation of GSK-3β resulting in the development of inflammation responses and liver damages during the development of ALF in mice.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Microbiology and Immunology Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Microbiology and Immunology Year: 2016 Type: Article