Lipid Based Therapy for Ulcerative Colitis—Modulation of Intestinal Mucus Membrane Phospholipids as a Tool to Influence InflammationReportar como inadecuado




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Department of Gastroenterology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany





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Abstract Ulcerative colitis UC is the result of an inappropriate colonic inflammatory response triggered by environmental and genetic factors. We have recently shown that mucus from UC patients has a decreased phosphatidylcholine PC content, while clinical trials revealed that therapeutic addition of PC to the colonic mucus alleviated the inflammatory activity. The mechanisms behind this are still unclear. We hypothesized that PC has at least two possible functions in the intestine: First, it establishes the surface hydrophobicity of the mucus and therefore protects the underlying tissue against intraluminal aggressors; recent experiments on surgical specimens revealed reduced surface tension and hydrophobicity in UC patients. Second, mucus phospholipids might also be integrated into the plasma membranes of enterocytes and thereby influence the signaling state of the mucosa. PC has been shown to inhibit TNF-α induced pro-inflammatory responses including: 1 assembly of plasma membrane actin; 2 activation of MAP kinases ERK and p38; and 3 activation of NF-κB and synthesis of pro-inflammatory gene products. Other phospholipids like phosphatidylethanolamine or sphingomyelin had no effect. PC also inhibited latex bead phagosome actin assembly, killing of M. tuberculosis in macrophages, and sphingosine-1-phosphate induced actin assembly in macrophages. Collectively, these results provide a molecular foundation that shows PC, firstly, as an anti-inflammatory, and secondly, as a surface hydrophobicity increasing compound with promising therapeutic potential in the treatment of inflammatory bowel disease. View Full-Text

Keywords: phospholipids; phosphatidylcholine; mucosal barrier; ulcerative colitis; phospholipase A2 phospholipids; phosphatidylcholine; mucosal barrier; ulcerative colitis; phospholipase A2





Autor: Hannah Schneider, Annika Braun, Joachim Füllekrug, Wolfgang Stremmel and Robert Ehehalt *

Fuente: http://mdpi.com/



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