The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro

Jennifer Y Kasper,1 Maria Iris Hermanns,1 Christian Cavelius,2 Annette Kraegeloh,2 Thomas Jung,3 Rolf Danzebrink,3 Ronald E Unger,1 Charles James Kirkpatrick1 1Institute of Pathology, University Medical Center, Mainz, 2Leibniz Institute for New Materials, 3NanoGate AG, Goettelborn, Saarbrüc...

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Autores principales:	Kasper JY, Hermanns MI, Cavelius C, Kraegeloh A, Jung T, Danzebrink R, Unger RE, Kirkpatrick CJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	intestinal microvasculature inflammatory bowel disease intestinal barrier in vitro Caco-2 ISO-HAS-1 inflammation nano-sized contrast agents Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fcd6f5c6a98541f79ba0efe7c6b8469e
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spelling	oai:doaj.org-article:fcd6f5c6a98541f79ba0efe7c6b8469e2021-12-02T02:04:23ZThe role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro1178-2013https://doaj.org/article/fcd6f5c6a98541f79ba0efe7c6b8469e2016-12-01T00:00:00Zhttps://www.dovepress.com/the-role-of-the-intestinal-microvasculature-in-inflammatory-bowel-dise-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jennifer Y Kasper,1 Maria Iris Hermanns,1 Christian Cavelius,2 Annette Kraegeloh,2 Thomas Jung,3 Rolf Danzebrink,3 Ronald E Unger,1 Charles James Kirkpatrick1 1Institute of Pathology, University Medical Center, Mainz, 2Leibniz Institute for New Materials, 3NanoGate AG, Goettelborn, Saarbrücken, Germany Abstract: The microvascular endothelium of the gut barrier plays a crucial role during inflammation in inflammatory bowel disease. We have modified a commonly used intestinal cell model based on the Caco-2 cells by adding microvascular endothelial cells (ISO-HAS-1). Transwell filters were used with intestinal barrier-forming Caco-2 cells on top and the ISO-HAS-1 on the bottom of the filter. The goal was to determine whether this coculture mimics the in vivo situation more closely, and whether the model is suitable to evaluate interactions of, for example, prospective nanosized drug vehicles or contrast agents with this coculture in a physiological and inflamed state as it would occur in inflammatory bowel disease. We monitored the inflammatory responsiveness of the cells (release of IL-8, soluble intercellular adhesion molecule 1, and soluble E-selectin) after exposure to inflammatory stimuli (lipopolysaccharide, TNF-α, INF-γ, IL1-β) and a nanoparticle (Ba/Gd: coprecipitated BaSO4 and Gd(OH)3), generally used as contrast agents. The barrier integrity of the coculture was evaluated via the determination of transepithelial electrical resistance and the apparent permeability coefficient (Papp) of NaFITC. The behavior of the coculture Caco-1/ISO-HAS-1 was compared to the respective monocultures Caco-2 and ISO-HAS-1. Based on transepithelial electrical resistance, the epithelial barrier integrity of the coculture remained stable during incubation with all stimuli, whereas the Papp decreased after exposure to the cytokine mixture (TNF-α, INF-γ, IL1-β, and Ba/Gd). Both the endothelial and epithelial monocultures showed a high inflammatory response in both the upper and lower transwell-compartments. However, in the coculture, inflammatory mediators were only detected on the epithelial side and not on the endothelial side. Thus in the coculture, based on the Papp, the epithelial barrier appears to prevent a potential inflammatory overreaction in the underlying endothelial cells. In summary, this coculture model exhibits in vivo-like features, which cannot be observed in conventional monocultures, making the former more suitable to study interactions with external stimuli. Keywords: intestinal microvasculature, inflammatory bowel disease, intestinal barrier in vitro, Caco-2, ISO-HAS-1, soluble E-selectin, sICAM-1, nanosized gadolinium contrast agentKasper JYHermanns MICavelius CKraegeloh AJung TDanzebrink RUnger REKirkpatrick CJDove Medical Pressarticleintestinal microvasculatureinflammatory bowel diseaseintestinal barrier in vitroCaco-2ISO-HAS-1inflammationnano-sized contrast agentsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6353-6364 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	intestinal microvasculature inflammatory bowel disease intestinal barrier in vitro Caco-2 ISO-HAS-1 inflammation nano-sized contrast agents Medicine (General) R5-920
spellingShingle	intestinal microvasculature inflammatory bowel disease intestinal barrier in vitro Caco-2 ISO-HAS-1 inflammation nano-sized contrast agents Medicine (General) R5-920 Kasper JY Hermanns MI Cavelius C Kraegeloh A Jung T Danzebrink R Unger RE Kirkpatrick CJ The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro
description	Jennifer Y Kasper,1 Maria Iris Hermanns,1 Christian Cavelius,2 Annette Kraegeloh,2 Thomas Jung,3 Rolf Danzebrink,3 Ronald E Unger,1 Charles James Kirkpatrick1 1Institute of Pathology, University Medical Center, Mainz, 2Leibniz Institute for New Materials, 3NanoGate AG, Goettelborn, Saarbrücken, Germany Abstract: The microvascular endothelium of the gut barrier plays a crucial role during inflammation in inflammatory bowel disease. We have modified a commonly used intestinal cell model based on the Caco-2 cells by adding microvascular endothelial cells (ISO-HAS-1). Transwell filters were used with intestinal barrier-forming Caco-2 cells on top and the ISO-HAS-1 on the bottom of the filter. The goal was to determine whether this coculture mimics the in vivo situation more closely, and whether the model is suitable to evaluate interactions of, for example, prospective nanosized drug vehicles or contrast agents with this coculture in a physiological and inflamed state as it would occur in inflammatory bowel disease. We monitored the inflammatory responsiveness of the cells (release of IL-8, soluble intercellular adhesion molecule 1, and soluble E-selectin) after exposure to inflammatory stimuli (lipopolysaccharide, TNF-α, INF-γ, IL1-β) and a nanoparticle (Ba/Gd: coprecipitated BaSO4 and Gd(OH)3), generally used as contrast agents. The barrier integrity of the coculture was evaluated via the determination of transepithelial electrical resistance and the apparent permeability coefficient (Papp) of NaFITC. The behavior of the coculture Caco-1/ISO-HAS-1 was compared to the respective monocultures Caco-2 and ISO-HAS-1. Based on transepithelial electrical resistance, the epithelial barrier integrity of the coculture remained stable during incubation with all stimuli, whereas the Papp decreased after exposure to the cytokine mixture (TNF-α, INF-γ, IL1-β, and Ba/Gd). Both the endothelial and epithelial monocultures showed a high inflammatory response in both the upper and lower transwell-compartments. However, in the coculture, inflammatory mediators were only detected on the epithelial side and not on the endothelial side. Thus in the coculture, based on the Papp, the epithelial barrier appears to prevent a potential inflammatory overreaction in the underlying endothelial cells. In summary, this coculture model exhibits in vivo-like features, which cannot be observed in conventional monocultures, making the former more suitable to study interactions with external stimuli. Keywords: intestinal microvasculature, inflammatory bowel disease, intestinal barrier in vitro, Caco-2, ISO-HAS-1, soluble E-selectin, sICAM-1, nanosized gadolinium contrast agent
format	article
author	Kasper JY Hermanns MI Cavelius C Kraegeloh A Jung T Danzebrink R Unger RE Kirkpatrick CJ
author_facet	Kasper JY Hermanns MI Cavelius C Kraegeloh A Jung T Danzebrink R Unger RE Kirkpatrick CJ
author_sort	Kasper JY
title	The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro
title_short	The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro
title_full	The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro
title_fullStr	The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro
title_full_unstemmed	The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro
title_sort	role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified caco-2 model including endothelial cells resembling the intestinal barrier in vitro
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/fcd6f5c6a98541f79ba0efe7c6b8469e
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The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro

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