Many signaling molecules involved in the pathogenesis of IBD, such as TNF or IFN, infections with bacteria or viruses and ionizing radiation, may cause an alteration of the lipid composition in the cell membrane by activation of sphingomyelinases (SMases). Activation of SMases is followed by rapid hydrolysis of plasma membrane sphingomyelin to the sphingolipid ceramide.
Permeability of the intestinal mucosa is controlled by a complex of proteins and lipids between cells, which is commonly described as tight-junction (TJ). TJs are rich in sphingomyelin and thus, the researchers hypothesized that hydrolysis of sphingomyelin to ceramide changes the composition of TJs and increases permeability of the intestinal epithelium.
To test this hypothesis, a research group led by Dr. Bock at University of Regensburg in Germany investigated the permeability of cell monolayers of intestinal epithelial cells with an in vitro model of the epithelial barrier. The addition of exogenous sphingomyelinase to the monolayers increased transepithelial permeability even at very low concentrations. Lipid analysis showed rapid accumulation of ceramide and a decrease in sphingomyelin and cholesterol in the membrane fractions containing TJ-proteins. Immunofluorescent staining confirmed clustering of ceramide at the sites of cell/cell contacts. Treatment of the monolayers with an anti-ceramide antibody prevented an increase of permeability by platelet activating factor, which is a lipid messenger known to increase permeability.
These findings indicate that SMase leads to localized accumulation of ceramide at the sites of cell/cell-contact with increased intestinal permeability. These changes could explain early disturbances of the epithelial barrier upon cellular stress deriving from toxic, infectious, inflammatory or radiogenic challenge to the intestinal epithelium.
Reference: Bock J, Liebisch G, Schweimer J, et al. Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function. World J Gastroenterology 2007; 13(39): 5217-5225 http://www.wjgnet.com/1007-9327/13/5217.asp
Correspondence to: J¨¹rgen Bock, MD, Department of Internal Medicine, University of Regensburg, Regensburg 93042, Germany. juergen.bock@klinik.uni-regensburg.de Telephone: +49-941-9447010 Fax: +49-941-9447073
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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection, and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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World Journal of Gastroenterology