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

Jennifer Y Kasper,C James Kirkpatrick,M Iris Hermanns,Annette Kraegeloh,Ronald E Unger,W Roth

doi:10.3390/ijms20133301

Abstract

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.

Highlights

Multicellular in vitro barrier models are increasingly being used in studies to evaluate, e.g., immune responses of the intestinal barrier after exposure to externally added stimuli
The intestinal microcirculation with its endothelial lining is being considered as a therapeutic point in inflammatory bowel disease (IBD), targeting, among others, leukocyte adhesion processes, ICAM-1 and E-selectin, whose expression patterns are induced in IBD [10]
Other studies have shown that the serum levels of the soluble forms of these adhesion molecules, sICAM-1 and sE-selectin, which are cleaved from the cell membrane, are elevated in IBD patients during inflammation

Summary

Introduction

Multicellular in vitro barrier models are increasingly being used in studies to evaluate, e.g., immune responses of the intestinal barrier after exposure to externally added stimuli. Other studies have shown that the serum levels of the soluble forms of these adhesion molecules, sICAM-1 and sE-selectin, which are cleaved from the cell membrane, are elevated in IBD patients during inflammation. These soluble forms are considered as serum biomarkers defining the severity of active IBD [11]. 100 nm to 1 μm in diameter) that bear ICAM-1 and E-selectin on their surface These endothelial microparticles (EMP) may serve as potential biomarkers for vascular injury. They can exhibit pro- as well as anti-inflammatory functions [12]

Methods

Results

Conclusion