Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn's mucosa through modulation of antioxidant defense machinery

• Published in: PloS one Vol. 7; no. 3; p. e32841
• Main Authors: Russo, Ilaria, Luciani, Alessandro, De Cicco, Paola, Troncone, Edoardo, Ciacci, Carolina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06-03-2012; Public Library of Science (PLoS)
• Subjects: Activation; Adolescent; Adult; Antioxidants; Antioxidants (Nutrients); Antioxidants - metabolism; Biology; Butyrates - pharmacology; Catalysis; Catalysis - drug effects; Catalytic activity; Cell Line; Colon; Confocal microscopy; Crohn Disease - immunology; Crohn Disease - pathology; Crohn's Disease; Crohns disease; Cyclooxygenase-2; E coli; Enzyme Activation - drug effects; Epithelial cells; Escherichia coli; Esters; Gastroenterology; Gastrointestinal diseases; Gene expression; Gene Expression - drug effects; Glutathione Transferase - genetics; Humans; Immune system; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory response; Intercellular adhesion molecule 1; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Intestine; Intracellular; Isoenzymes - genetics; Kinases; Lamina propria; Leukocytes (mononuclear); Lipopolysaccharides; Lipopolysaccharides - immunology; Machinery and equipment; MAP kinase; Medicine; Metabolism; Microscopy; Mitogens; Mucosa; NF-kappa B - metabolism; NF-κB protein; Oxidation-Reduction; Oxidative Stress; Oxygen; Pathogenesis; Patients; Phosphorylation; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; RNA; RNA, Messenger - metabolism; Rodents; Studies; Young Adult; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032841

Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB), which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia coli (EC-LPS) in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa.