Journal article
Retinoic acid improves baseline barrier function and attenuates TNF-α-induced barrier leak in human bronchial epithelial cell culture model, 16HBE 14o-
PLOS ONE, v 15(12), e0242536
10 Dec 2020
PMID: 33301441
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Retinoic acid (RA) has been shown to improve epithelial and endothelial barrier function and development and even suppress damage inflicted by inflammation on these barriers through regulating immune cell activity. This paper thus sought to determine whether RA could improve baseline barrier function and attenuate TNF-alpha-induced barrier leak in the human bronchial epithelial cell culture model, 16HBE14o- (16HBE). We show for the first time that RA increases baseline barrier function of these cell layers indicated by an 89% increase in transepithelial electrical resistance (TER) and 22% decrease in C-14-mannitol flux. A simultaneous, RA-induced 70% increase in claudin-4 attests to RA affecting the tight junctional (TJ) complex itself. RA was also effective in alleviating TNF-alpha-induced 16HBE barrier leak, attenuating 60% of the TNF-alpha-induced leak to C-14-mannitol and 80% of the leak to C-14-inulin. Interleukin-6-induced barrier leak was also reduced by RA. Treatment of 16HBE cell layers with TNF-alpha resulted in dramatic decrease in immunostaining for occludin and claudin-4, as well as a downward band-shift in occludin Western immunoblots. The presence of RA partially reversed TNF-alpha's effects on these select TJ proteins. Lastly, RA completely abrogated the TNF-alpha-induced increase in ERK-1,2 phosphorylation without significantly decreasing the TNF-driven increase in total ERK-1,2. This study suggests RA could be effective as a prophylactic agent in minimizing airway barrier leak and as a therapeutic in preventing leak triggered by inflammatory cascades. Given the growing literature suggesting a cytokine storm may be related to COVID-19 morbidity, RA may be a useful adjuvant for use with anti-viral therapies.
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Details
- Title
- Retinoic acid improves baseline barrier function and attenuates TNF-α-induced barrier leak in human bronchial epithelial cell culture model, 16HBE 14o-
- Publication Details
- PLOS ONE, v 15(12), e0242536
- Publisher
- PUBLIC LIBRARY SCIENCE; SAN FRANCISCO
- Grant note
- This work was supported in part by NIH grant 1R21AI139392-01 (PI: JMM).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000600143100012
- Scopus ID
- 2-s2.0-85097828579
- Other Identifier
- 991021860776204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology