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.
ISSN 0036-5521, 1502-7708
Abstract
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: | 22 May 2026 16:25 |
| DOI: | 10.1080/00365521.2018.1458146 |
| Open Access URL: | https://www.tandfonline.com/doi/full/10.1080/00365... |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3021666 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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