Supplementary Material for: The Detergent Effect of Mesalazine Interferes with Phosphatidylcholine Binding to Mucin 2 Stremmel W. Staffer S. Gehrke S. 10.6084/m9.figshare.7223150.v1 https://karger.figshare.com/articles/dataset/Supplementary_Material_for_The_Detergent_Effect_of_Mesalazine_Interferes_with_Phosphatidylcholine_Binding_to_Mucin_2/7223150 <b><i>Objectives:</i></b><i></i> Therapeutically applied delayed-release phosphatidylcholine (PC) revealed mucosa protection and clinical improvement of ulcerative colitis. However, a recent trial with simultaneous application of delayed-release PC and mesalazine showed lack of efficacy. It is hypothesized that mesalazine acts as detergent to prohibit PC integration into mucus as target compartment, thus preventing topical mucus protection. <b><i>Methods:</i></b> In vitro PC-binding studies with mucin 2 and intestinally differentiated CaCo2 cells as well as outcome analysis of a therapeutic trial with delayed-release PC and additional mesalazine. <b><i>Results:</i></b> Choline-containing phospholipids, in particular PC, bind to mucin 2 as main scaffold protein of intestinal mucus to establish a hydrophobic barrier towards microbiota in the intestinal lumen. PC also binds to the apical surface of polarized CaCo2 cells with membrane-anchored mucin 3. Mesalazine removes mucin-bound PC and, thus, reduces transepithelial resistance. A post hoc analysis of patients from a previous multicenter phase IIB trial with delayed-release PC revealed that those without mesalazine showed a PC dose-dependent outcome with regard to achievement of partial and complete remission (<i>p</i> < 0.05 for 1.6 and 3.2 g PC daily) whereas those treated simultaneously with mesalazine showed no PC dose dependency. <b><i>Conclusion:</i></b> Mesalazine solubilizes PC and, thus, prevents the protective action of therapeutically applied delayed-release PC within mucus. 2018-10-18 08:19:40 CaCo2 cells Mesalazine Mucin 2 Phosphatidylcholine Ulcerative colitis