TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Kasper, Jennifer Y.
A1  - Hermanns, Maria Iris
A1  - Kraegeloh, Annette
A1  - Roth, W.
A1  - Kirkpatrick, C. James
A1  - Unger, Ronald E.
T1  - In Vitro Entero-Capillary Barrier Exhibits Altered Inflammatory and Exosomal Communication Pattern after Exposure to Silica Nanoparticles
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - intestinal microvasculature
KW  - inflammatory bowel disease
KW  - intestinal barrier in vitro
KW  - Caco-2
KW  - ISO-HAS-1
KW  - soluble E-selection
KW  - sICAM-1
KW  - exosomes
KW  - silica nanoparticles
KW  - SIRS
Y1  - 2019
UN  - https://nbn-resolving.org/urn:nbn:de:bsz:291:415-3776
UR  - https://www.mdpi.com/1422-0067/20/13/3301
SN  - 1422-0067
SS  - 1422-0067
U6  - https://doi.org/10.3390/ijms20133301
DO  - https://doi.org/10.3390/ijms20133301
VL  - 20
IS  - 13
SP  - 3301
S1  - 3301
ER  -