Chromatin modifications via histone deacetylation regulate the inflammatory response in lipopolysaccharide (LPS)-stimulated immune cells from patients with advanced cirrhosis

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Correlational selection on pro- and anti-inflammatory effectors.

9 pagesInternational audienceParasites impose a permanent threat for hosts. As a consequence, immune defenses are important for host fitness. However, the immune response can also produce self-damage and impair host fitness if not properly regulated. Effectors that up- and downregulate the immune response should, therefore, evolve in concert, and be under the action of correlational selection. To address this issue, we assessed the shape of the selection operating on pro- and anti-inflammatory effectors following an inflammatory challenge in laboratory mice. We found that selection acts on the combination of these two traits as individuals that produced large amount of pro-inflammatory cytokines could achieve relatively high fitness (survival) only if also producing a large amount of anti-inflammatory effectors. To our knowledge, this is the first study providing evidence for correlational selection on immunity

Lysine acetylation plays a major role in the regulation of the innate TLR4-mediated inflammatory response in patients with cirrhosis

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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

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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