Anti-inflammatory and anti-angiogenic effect of long chain n-3 polyunsaturated fatty acids in intestinal microvascular endothelium |
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Authors: | Ibrahim Ayman Mbodji Khaly Hassan Aktham Aziz Moutaz Boukhettala Nabile Coëffier Moïse Savoye Guillaume Déchelotte Pierre Marion-Letellier Rachel |
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Affiliation: | aAppareil Digestif Environnement Nutrition (ADEN EA 4311), Medicine, University of Rouen, I.F.R. 23, Institute of Biomedical Research, 22 boulevard Gambetta, 76183 Rouen cedex, France;bLaboratory of Anatomo-Pathology, Rouen University Hospital, France;cNutrition Unit, Rouen University Hospital, 1 rue de Germont, 76031 Rouen cedex, France;dDepartment of Gastroenterology, Rouen University Hospital, 1 rue de Germont, 76031 Rouen cedex, France |
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Abstract: | Background & aimsThe role of endothelial cells in inflammatory bowel disease has been recently emphasized. Endothelial activation and expression of adhesion molecules are critical for leukocytes recruitment into the inflammatory wall. Compelling evidence demonstrated anti-inflammatory effects of long chain n-3 PUFA in inflammatory models. We previously showed that long chain n-3 PUFA (EPA and DHA) inhibited inflammatory response in epithelial and dendritic cells. As long chain n-3 PUFA treatment led to a decreased expression of adhesion molecules in endothelial cells from other organs, we have now investigated their effect on intestinal endothelial cells in vitro and in colitic rats.MethodsIn vitro study: Primary culture of human intestinal microvascular endothelial cells (HIMEC) were pre-treated with DHA and then incubated with IL-1β. In vivo study: Colitis was induced in 2 groups at day0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS). Rats received by gavage either fish oil, rich in EPA and DHA (TNBS+n-3) or an isocaloric isolipidic oil formula for 14 days.ResultsDHA led to a decreased VCAM-1, TLR4, cyclooxygenase-2 and VEGFR2 expression and a decreased production of IL-6, IL-8 and GM-CSF and a reduced production of PGE2 and LTB4 (p < 0.001) in IL-1β-induced HIMEC. Similarly, dietary intervention with fish oil rich in EPA and DHA significantly decreased colon production of PGE2 and LTB4, endothelial VCAM-1 and VEGFR2 in rats with colitis.ConclusionsData obtained from in vitro and in vivo studies reveal a potential anti-angiogenic role of long chain n-3 PUFA in intestinal endothelial cells. This protective effect of long chain n-3 PUFA may partly explain the observed benefit of dietary intake of long chain n-3 PUFA in IBD development. |
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Keywords: | Colitis Endothelium HIMEC Inflammation n-3 PUFA |
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