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Media type:
E-Article
Title:
The Detergent Effect of Mesalazine Interferes with Phosphatidylcholine Binding to Mucin 2
Contributor:
Stremmel, Wolfgang;
Staffer, Simone;
Gehrke, Sven
Published:
S. Karger AG, 2018
Published in:
Inflammatory Intestinal Diseases, 3 (2018) 3, Seite 107-115
Language:
English
DOI:
10.1159/000493347
ISSN:
2296-9403;
2296-9365
Origination:
Footnote:
Description:
<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> &#x3c; 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.