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Infliximab restores...
Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts
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- Yakymenko, Olena, 1988- (author)
- Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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- Schoultz, Ida, 1979- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Faculty of Health and Medicine, Örebro University, Örebro, Sweden
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- Gullberg, Elisabet, 1972- (author)
- 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- (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Magtarmmedicinska kliniken,Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden
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- Almer, Sven (author)
- Karolinska Institutet,Department of Medicine, Karolinska Institutet, Stockholm, Sweden / GastroCentrum, Karolinska University Hospital, Stockholm, Sweden
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- Wallon, Conny, 1966- (author)
- 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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- Wang, Arthur (author)
- Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada.
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- Keita, Åsa, 1973- (author)
- 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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- Campbell, Barry J. (author)
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
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- McKay, Derek M. (author)
- Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada
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- Söderholm, Johan D, 1958- (author)
- 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
- English.
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In: Scandinavian Journal of Gastroenterology. - Oxfordshire, United Kingdom : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 53:6, s. 677-684
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- Inflammatory bowel disease
- microbiology
- large intestine
- intestinal barrier function
- adherent invasive E. coli
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Yakymenko, Olena ...
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Schoultz, Ida, 1 ...
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Gullberg, Elisab ...
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Ström, Magnus, 1 ...
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Almer, Sven
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Wallon, Conny, 1 ...
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Wang, Arthur
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Keita, Åsa, 1973 ...
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Campbell, Barry ...
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McKay, Derek M.
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Söderholm, Johan ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
- Articles in the publication
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Scandinavian Jou ...
- By the university
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Linköping University
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Örebro University
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Karolinska Institutet