Abstract

Intestinal epithelial cell (IEC) junctions constitute a robust barrier to invasion by viruses, bacteria and exposure to ingested agents. Previous studies showed that microgravity compromises the human immune system and increases enteropathogen virulence. However, the effects of microgravity on epithelial barrier function are poorly understood. The aims of this study were to identify if simulated microgravity alters intestinal epithelial barrier function (permeability), and susceptibility to barrier-disrupting agents. IECs (HT-29.cl19a) were cultured on microcarrier beads in simulated microgravity using a rotating wall vessel (RWV) for 18 days prior to seeding on semipermeable supports to measure ion flux (transepithelial electrical resistance (TER)) and FITC-dextran (FD4) permeability over 14 days. RWV cells showed delayed apical junction localization of the tight junction proteins, occludin and ZO-1. The alcohol metabolite, acetaldehyde, significantly decreased TER and reduced junctional ZO-1 localization, while increasing FD4 permeability in RWV cells compared with static, motion and flask control cells. In conclusion, simulated microgravity induced an underlying and sustained susceptibility to epithelial barrier disruption upon removal from the microgravity environment. This has implications for gastrointestinal homeostasis of astronauts in space, as well as their capability to withstand the effects of agents that compromise intestinal epithelial barrier function following return to Earth.

Details

Title
A Simulated Microgravity Environment Causes a Sustained Defect in Epithelial Barrier Function
Author
Alvarez, Rocio 1 ; Stork, Cheryl A 2 ; Sayoc-Becerra, Anica 3 ; Marchelletta, Ronald R 4 ; G Kim Prisk 5 ; McCole, Declan F 3   VIAFID ORCID Logo 

1  Division of Biomedical Sciences, University of California, Riverside, Riverside, CA, USA; Cedars-Sinai Medical Center, Los Angeles, CA, USA 
2  Division of Biomedical Sciences, University of California, Riverside, Riverside, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA 
3  Division of Biomedical Sciences, University of California, Riverside, Riverside, CA, USA 
4  Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Johnson & Johnson Research Laboratories, Janssen Pharmaceuticals Inc., La Jolla, CA, USA 
5  Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA 
Pages
1-15
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-53862-3
ProQuest document ID
2318700499
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.