Unrestricted constitutive activity of glycogen synthase kinasde 3 (GSK3) inhibits anti-inflammatory and favors pro-inflammatory cytokine production in LPS-stimulated immune cells from patients with advanced cirrhosis

info:eu-repo/semantics/publishe

Glycogen synthase kinase 3 involvement in the excessive proinflammatory response to LPS in patients with decompensated cirrhosis.

In decompensated cirrhosis, the early innate immune response to the Toll-like receptor 4 (TLR4) agonist, lipopolysaccharides (LPS), is characterized by a hyper-production of pro-inflammatory cytokines and hypo-production of the anti-inflammatory cytokine IL-10. In LPS-stimulated non-cirrhotic immune cells, the constitutively active glycogen synthase kinase (GSK) 3 favors pro- vs. anti-inflammatory cytokines, by acting on gene induction. However, in these cells, TLR4 dampens its own pro-inflammatory response by inducing early (within minutes) AKT-mediated phosphorylation of GSK3β (one of two GSK3 isoforms) on Ser9. Phosphorylation of GSK3β (Ser9) inhibits its activity, decreases pro-inflammatory cytokines, and increases IL-10. Thus, we investigated the role of GSK3 in LPS-induced cytokine production by peripheral blood mononuclear cells (PBMCs) or monocytes from patients with advanced cirrhosis and normal subjects.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Gene- and exon-expression profiling reveals an extensive LPS-induced response in immune cells in patients with cirrhosis.

Lipopolysaccharide (LPS)-expressing bacteria cause severe inflammation in cirrhotic patients. The global gene response to LPS is unknown in cirrhotic immune cells.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe