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Open AccessArticle

In Vitro Entero-Capillary Barrier Exhibits Altered Inflammatory and Exosomal Communication Pattern after Exposure to Silica Nanoparticles

1
Institute of Pathology, University Medical Center, 55131 Mainz, Germany
2
INM, Leibniz Institute for New Materials, D-66123 Saarbrücken, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3301; https://doi.org/10.3390/ijms20133301
Received: 28 May 2019 / Revised: 25 June 2019 / Accepted: 1 July 2019 / Published: 5 July 2019
(This article belongs to the Special Issue Endothelial Dysfunction: Pathophysiology and Molecular Mechanisms)
The intestinal microvasculature (iMV) plays multiple pathogenic roles during chronic inflammatory bowel disease (IBD). The iMV acts as a second line of defense and is, among other factors, crucial for the innate immunity in the gut. It is also the therapeutic location in IBD targeting aggravated leukocyte adhesion processes involving ICAM-1 and E-selectin. Specific targeting is stressed via nanoparticulate drug vehicles. Evaluating the iMV in enterocyte barrier models in vitro could shed light on inflammation and barrier-integrity processes during IBD. Therefore, we generated a barrier model by combining the enterocyte cell line Caco-2 with the microvascular endothelial cell line ISO-HAS-1 on opposite sides of a transwell filter-membrane under culture conditions which mimicked the physiological and inflamed conditions of IBD. The IBD model achieved a significant barrier-disruption, demonstrated via transepithelial-electrical resistance (TER), permeability-coefficient (Papp) and increase of sICAM sE-selectin and IL-8. In addition, the impact of a prospective model drug-vehicle (silica nanoparticles, aSNP) on ongoing inflammation was examined. A decrease of sICAM/sE-selectin was observed after aSNP-exposure to the inflamed endothelium. These findings correlated with a decreased secretion of ICAM/E-selectin bearing exosomes/microvesicles, as evaluated via ELISA. Our findings indicate that aSNP treatment of the inflamed endothelium during IBD may hamper exosomal/microvesicular systemic communication. View Full-Text
Keywords: intestinal microvasculature; inflammatory bowel disease; intestinal barrier in vitro; Caco-2; ISO-HAS-1; soluble E-selectin; sICAM-1; exosomes; silica nanoparticles; SIRS intestinal microvasculature; inflammatory bowel disease; intestinal barrier in vitro; Caco-2; ISO-HAS-1; soluble E-selectin; sICAM-1; exosomes; silica nanoparticles; SIRS
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Kasper, J.Y.; Hermanns, M.I.; Kraegeloh, A.; Roth, W.; Kirkpatrick, C.J.; Unger, R.E. In Vitro Entero-Capillary Barrier Exhibits Altered Inflammatory and Exosomal Communication Pattern after Exposure to Silica Nanoparticles. Int. J. Mol. Sci. 2019, 20, 3301.

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