Modulating the Barrier Function of Human Alveolar Epithelial (hAELVi) Cell Monolayers as a Model of Inflammation. Issue 5 (September 2020)

• Record Type: Journal Article
• Authors: Metz, Julia Katharina; Wiegand, Birgit; Schnur, Sabrina; Knoth, Katharina; Schneider-Daum, Nicole; Groß, Henrik; Croston, Glenn; Reinheimer, Torsten Michael; Lehr, Claus-Michael; Hittinger, Marius
• Is Part Of: ATLA. Volume 48:Issue 5/6(2020)
• Page Start: 252
• Page End: 267
• Publication Date: 2020-09
• Subjects: alveolar epithelium -- ARDS -- hydrocortisone -- paracellular permeability -- TEER -- Three Rs; Laboratory animals -- Periodicals; 616.0273
• DOI: 10.1177/0261192920983015
• Languages: English
• ISSNs: 0261-1929

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.