Modulating the Barrier Function of Human Alveolar Epithelial (hAELVi) Cell Monolayers as a Model of Inflammation

Author:

Metz Julia Katharina12,Wiegand Birgit1,Schnur Sabrina12,Knoth Katharina1,Schneider-Daum Nicole3,Groß Henrik1,Croston Glenn4,Reinheimer Torsten Michael5,Lehr Claus-Michael23,Hittinger Marius16

Affiliation:

1. PharmBioTec GmbH, Saarbrücken, Germany

2. Department of Pharmacy, Saarland University, Saarbrücken, Germany

3. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany

4. Croston Consulting, San Diego, CA, USA

5. Department of Non-Clinical Development, Ferring Pharmaceuticals A/S, Copenhagen, Denmark

6. 3RProducts Marius Hittinger, Blieskastel, Germany

Abstract

The incidence of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) remains an important problem, particularly in the present time with the Covid-19 pandemic. However, an adequate in vitro test system to monitor the barrier function of the alveolar epithelium during inflammation and for assessing anti-inflammatory drugs is urgently needed. Therefore, we treated human Alveolar Epithelial Lentivirus-immortalised cells (hAELVi cells) with the pro-inflammatory cytokines TNF-α (25 ng/ml) and IFN-γ (30 ng/ml), in the presence or absence of hydrocortisone (HC). While TNF-α and IFN-γ are known to reduce epithelial barrier properties, HC could be expected to protect the barrier function and result in an anti-inflammatory effect. We investigated the impact of anti-inflammatory/inflammatory treatment on transepithelial electrical resistance (TEER) and the apparent permeability coefficient (P app) of the low permeability marker sodium fluorescein (NaFlu). After incubating hAELVi cells for 48 hours with a combination of TNF-α and IFN-γ, there was a significant decrease in TEER and a significant increase in the P app. The presence of HC maintained the TEER values and barrier properties, so that no significant P app change was observed. By using hAELVi cells to study anti-inflammatory drugs in vitro, the need for animal experiments could be reduced and pulmonary drug development accelerated.

Funder

Bundesministerium für Bildung und Forschung

Publisher

SAGE Publications

Subject

Medical Laboratory Technology,Toxicology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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