T1686 Carrageenan-Mediated Increases in NfκB Involve the Ikkα, β, and γ Components of the Ikk Signalosome

Abstract

INTRODUCTION: An involvement of the intestinal lymphatic systemhas been long suggested in IBD(1). New markers have become available to distinguish lymphatic vessels from blood vessels. AIMS & METHODS: The aim of the study was to examine the distribution of lymphatic vessels within macroscopically inflamed and non-inflamed colonic mucosa of IBD patients (18 CD, 17 ulcerative colitis (UC)) and compare it with healthy controls (9) using immunohistochemistry and real-time PCR for podoplanin. Quantification of lymphatic vessels was performed on podoplanin stained sections using Weibel graticule in 7 fields randomly selected in all patients. Lymphatic vessel density was expressed as mean ±SEM surface area (SA). Levels of podoplanin mRNA were expressed as relative mean ±SEM unit. For statistical analysis, a permutation test was used. RESULTS: In CD patients, the number of lymphatics was significantly increased in non-inflamed (SA 1.89%±0.28, p <0.01) and inflamed colonic mucosa (SA 3.0%±0.30, p<0.001) compared to controls (SA 0.36%±0.14). Podoplanin mRNA levels were similar in non inflamed areas (13.75±1.97, NS) compared to controls (11.98±3.13) whereas a six fold increase was seen in inflamed areas (74.70±29.80, p<0.05). In UC patients, the number of lymphatics was significantly increased in non-inflamed (SA 2.38%±0.27, p<0.001) and inflamed colonic mucosa (SA 2.77%±0.28, p<0.001) compared to controls (SA 0.36%±0.14). An increase in podoplanin mRNA levels was seen both in non inflamed (17.42±6.72, NS) and inflamed areas (117.43±39, p<0.01) compared to controls (11.98±3.13). In control patients, lymphatics were only present close to or under the muscularis mucosae contrasting with a diffuse presence throughout the mucosa in both CD and UC patients. CONCLUSION: A strong lymphangiogenesis occurs within the colonic mucosa of IBD patients together with a change in distribution and appearance of lymphatics in the upper half of the lamina propria. The present data further suggest that lymphangiogenesis play a role in the pathogenesis of IBD. Furthermore, this distribution challenges the established dogma stating the lack of lymphatic vessels in colonic mucosa. (1)Van Kruiningen HJ, Colombel JF. The forgotten role of lymphangitis in Crohn's disease. Gut 2008;57:1-4.