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

  • 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.

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Document Type:Article
Author:Jennifer Y. Kasper, Marina Iris Hermanns, Annette KraegelohORCiD, W. Roth, C. James KirkpatrickORCiD, Ronald E. Unger
Parent Title (English):International Journal of Molecular Sciences
Year of first Publication:2019
Release Date:2022/11/18
Tag:Caco-2; ISO-HAS-1; SIRS; exosomes; inflammatory bowel disease; intestinal barrier in vitro; intestinal microvasculature; sICAM-1; silica nanoparticles; soluble E-selection
Impact:04.556 (2019)
Funding Information:BMBF- initiative: „Sicherer Umgang mit synthetischen Nanomaterialien—Erforschung der Auswirkungen auf den Menschen und die Umwelt—NanoCare“ within the framework program, Werkstoffinnovationen für Industrie und Gesellschaft—WING“—Konsortium: NanoKon.
Groups:Nano Zell Interaktionen
Open Access:Open Access
Signature:INM 2019/094
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International