TY  - JOUR
A1  - Bärnthaler, Thomas
A1  - Maric, Jovana
A1  - Platzer, Wolfgang
A1  - Konya, Viktoria
A1  - Theiler, Anna
A1  - Hasenöhrl, Carina
A1  - Gottschalk, Benjamin
A1  - Trautmann, Sandra
A1  - Schreiber, Yannick
A1  - Graier, Wolfgang F.
A1  - Schicho, Rudolf
A1  - Marsche, Gunther
A1  - Olschewski, Andrea
A1  - Thomas, Dominique Jeanette
A1  - Schuligoi, Rufina
A1  - Heinemann, Akos
T1  - The role of PGE2 in alveolar epithelial and lung microvascular endothelial crosstalk
T2  - Scientific reports
N2  - Disruption of the blood-air barrier, which is formed by lung microvascular endothelial and alveolar epithelial cells, is a hallmark of acute lung injury. It was shown that alveolar epithelial cells release an unidentified soluble factor that enhances the barrier function of lung microvascular endothelial cells. In this study we reveal that primarily prostaglandin (PG) E2 accounts for this endothelial barrier-promoting activity. Conditioned media from alveolar epithelial cells (primary ATI-like cells) collected from BALB/c mice and A549 cells increased the electrical resistance of pulmonary human microvascular endothelial cells, respectively. This effect was reversed by pretreating alveolar epithelial cells with a cyclooxygenase-2 inhibitor or by blockade of EP4 receptors on endothelial cells, and in A549 cells also by blocking the sphingosine-1-phosphate1 receptor. Cyclooxygenase-2 was constitutively expressed in A549 cells and in primary ATI-like cells, and was upregulated by lipopolysaccharide treatment. This was accompanied by enhanced PGE2 secretion into conditioned media. Therefore, we conclude that epithelium-derived PGE2 is a key regulator of endothelial barrier integrity via EP4 receptors under physiologic and inflammatory conditions. Given that pharmacologic treatment options are still unavailable for diseases with compromised air-blood barrier, like acute lung injury, our data thus support the therapeutic potential of selective EP4 receptor agonists.
KW  - Acute inflammation
KW  - Respiration
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43958
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439584
SN  - 2045-2322
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
VL  - 7
IS  - 1, Art. 7923
SP  - 1
EP  - 17
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -