Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn’s disease via effects on epithelial lipid rafts

Yakymenko, Olena, Schoultz, Ida, Gullberg, Elisabeth, Ström, Magnus, Almer, Sven, Wallon, Conny, Wang, Arthur, Keita, Åsa V, Campbell, Barry J ORCID: 0000-0002-7407-012X, McKay, Derek M
et al (show 1 more authors) (2018) Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn’s disease via effects on epithelial lipid rafts. Scandinavian journal of gastroenterology, 53 (6). pp. 677-684.

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Objective: Infliximab is important in the therapeutic arsenal of Crohn’s disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa. Materials and methods: Endoscopic biopsies from non-inflamed colon of seven patients with CD, before and after two infliximab infusions, and eight non-inflammation controls, were mounted in Ussing chambers. Paracellular permeability (51Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors. Results: Before infliximab treatment, colonic passage of HM427 [CD: 2475 CFU (450–3000); controls 1163(225–1950)] and 51Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8–1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport. Conclusion: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab’s clinical efficacy in colonic CD.

Item Type: Article
Uncontrolled Keywords: Inflammatory bowel disease, Microbiology, Large intestine, Intestinal barrier function, Adherent invasive E. coli
Depositing User: Symplectic Admin
Date Deposited: 23 May 2018 14:23
Last Modified: 19 Jan 2023 01:33
DOI: 10.1080/00365521.2018.1458146
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