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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 universitet, Institutionen för medicinska vetenskaper. 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.
Vise andre og tillknytning
2018 (engelsk)Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 6, s. 677-684Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
Oxfordshire, United Kingdom: Taylor & Francis, 2018. Vol. 53, nr 6, s. 677-684
Emneord [en]
Inflammatory bowel disease: microbiology: large intestine: intestinal barrier function: adherent invasive E: coli
HSV kategori
Identifikatorer
URN: urn:nbn:se:oru:diva-66790DOI: 10.1080/00365521.2018.1458146ISI: 000438146900008PubMedID: 29688802Scopus ID: 2-s2.0-85046040952OAI: oai:DiVA.org:oru-66790DiVA, id: diva2:1201946
Forskningsfinansiär
Swedish Research Council, VR-MH 2014-02537
Merknad

Funding Agency:

ALF Grants Region Östergötland

Tilgjengelig fra: 2018-04-27 Laget: 2018-04-27 Sist oppdatert: 2018-07-27bibliografisk kontrollert

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