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World J Gastroenterol. Mar 14, 2008; 14(10): 1528-1533
Published online Mar 14, 2008. doi: 10.3748/wjg.14.1528
Increased basolateral sorting of carcinoembryonic antigen in a polarized colon carcinoma cell line after cholesterol depletion-Implications for treatment of inflammatory bowel disease
Robert Ehehalt, Markus Krautter, Martin Zorn, Richard Sparla, Joachim Füllekrug, Hasan Kulaksiz, Wolfgang Stremmel
Robert Ehehalt, Markus Krautter, Richard Sparla, Joachim Füllekrug, Hasan Kulaksiz, Wolfgang Stremmel, Department of Gastroenterology, Hepatology and Infectious diseases, University of Heidelberg, INF 410, Heidelberg 69120, Germany
Martin Zorn, Central Laboratory Unit, University of Heidelberg, INF 410, Heidelberg 69120, Germany
Author contributions: Ehehalt R, Krautter M, Stremmel W and Füllekrug J designed research; Ehehalt R, Krautter M, Sparla R and Kulaksiz H performed research; Zorn M contributed new reagents/analytic tools; Ehehalt R, and Krautter M analyzed data; and Ehehalt R wrote the paper.
Correspondence to: Robert Ehehalt, MD, Department of Internal Medicine IV University Hospital, INF410, Heidelberg 69120, Germany. robert_ehehalt@urz.uni-heidelberg.de
Telephone: +49-6221-5638715
Received: September 27, 2007
Revised: December 15, 2007
Published online: March 14, 2008
Abstract

AIM: To investigate a possible increase of basolateral expression of carcinoembryonic antigen (CEA) by interfering with the apical transport machinery, we studied the effect of cholesterol depletion on CEA sorting and secretion.

METHODS: Cholesterol depletion was performed in polarized Caco-2 cells using lovastatin and methyl-β-cyclodextrin.

RESULTS: We show that CEA is predominantly expressed and secreted at the apical surface. Reduction of the cholesterol level of the cell by 40%-50% with lovastatin and methyl-β-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane.

CONCLUSION: As basolateral expression of CEA has been suggested to have anti-inflammatory properties, Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

Keywords: Inflammatory bowel disease; Cholesterol; Polarized secretion; Carcinoembryonic antigen; Caco-2