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Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts
Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Örebro University, School of Medical Sciences. Department of Medical Sciences.ORCID iD: 0000-0002-8391-1576
Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden.
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, p. 1-8Article in journal (Refereed) Epub ahead of print
Abstract [en]

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: Cr-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: Cr-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.

Place, publisher, year, edition, pages
Oxfordshire, United Kingdom: Taylor & Francis, 2018. p. 1-8
Keywords [en]
Inflammatory bowel disease, adherent invasive E. coli, intestinal barrier function, large intestine, microbiology
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-66790DOI: 10.1080/00365521.2018.1458146PubMedID: 29688802OAI: oai:DiVA.org:oru-66790DiVA, id: diva2:1201946
Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2018-05-04Bibliographically approved

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Schoultz, Ida

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