The Detergent Effect of Mesalazine Interferes with Phosphatidylcholine Binding to Mucin 2.
Inflamm Intest Dis
; 3(3): 107-115, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30820432
ABSTRACT
OBJECTIVES:
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.METHODS:
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.RESULTS:
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 (p < 0.05 for 1.6 and 3.2 g PC daily) whereas those treated simultaneously with mesalazine showed no PC dose dependency.CONCLUSION:
Mesalazine solubilizes PC and, thus, prevents the protective action of therapeutically applied delayed-release PC within mucus.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
Idioma:
En
Revista:
Inflamm Intest Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha