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

Yakymenko, Olena, 1988- (författare)
Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Schoultz, Ida, 1979- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Faculty of Health and Medicine, Örebro University, Örebro, Sweden
Gullberg, Elisabet, 1972- (författare)
Linköpings universitet,Medicinska fakulteten,Institutionen för klinisk och experimentell medicin,Region Östergötland, Kirurgiska kliniken US,Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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Ström, Magnus, 1945- (författare)
Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Magtarmmedicinska kliniken,Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden
Almer, Sven (författare)
Karolinska Institutet,Department of Medicine, Karolinska Institutet, Stockholm, Sweden / GastroCentrum, Karolinska University Hospital, Stockholm, Sweden
Wallon, Conny, 1966- (författare)
Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US,Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Wang, Arthur (författare)
Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Keita, Åsa, 1973- (författare)
Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US,Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Campbell, Barry J. (författare)
Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
McKay, Derek M. (författare)
Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada
Söderholm, Johan D, 1958- (författare)
Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US,Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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 (creator_code:org_t)
2018-04-24
2018
Engelska.
Ingår i: Scandinavian Journal of Gastroenterology. - Oxfordshire, United Kingdom : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 53:6, s. 677-684
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

Nyckelord

Inflammatory bowel disease
microbiology
large intestine
intestinal barrier function
adherent invasive E. coli

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