Butyrate Attenuates Lipopolysaccharide-Induced Inflammation in Intestinal Cells and Crohns Mucosa through Modulation of Antioxidant Defense MachineryReport as inadecuate




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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.



Author: Ilaria Russo, Alessandro Luciani, Paola De Cicco, Edoardo Troncone, Carolina Ciacci

Source: http://plos.srce.hr/



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