Back to Search
Start Over
GSK-3β inhibition attenuates CLP-induced liver injury by reducing inflammation and hepatic cell apoptosis.
- Source :
-
Mediators of inflammation [Mediators Inflamm] 2014; Vol. 2014, pp. 629507. Date of Electronic Publication: 2014 Nov 30. - Publication Year :
- 2014
-
Abstract
- Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK-) 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP), and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB) but enhanced the transcriptional activity of cAMP response element binding protein (CREB) in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.
- Subjects :
- Animals
Cell Line
Cytokines metabolism
Enzyme-Linked Immunosorbent Assay
Glycogen Synthase Kinase 3 beta
Immunohistochemistry
Indoles chemistry
Interleukin-6 metabolism
Leukocytes cytology
Liver injuries
Liver metabolism
Male
Maleimides chemistry
Mice
Mice, Inbred C57BL
NF-kappa B metabolism
Peroxidase metabolism
Signal Transduction
Apoptosis
Glycogen Synthase Kinase 3 metabolism
Inflammation metabolism
Liver pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1466-1861
- Volume :
- 2014
- Database :
- MEDLINE
- Journal :
- Mediators of inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 25525303
- Full Text :
- https://doi.org/10.1155/2014/629507