A Simulated Microgravity Environment Causes a Sustained Defect in Epithelial Barrier Function

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 epith...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2019-11, Vol.9 (1), p.17531-15, Article 17531
Main Authors: Alvarez, Rocio, Stork, Cheryl A., Sayoc-Becerra, Anica, Marchelletta, Ronald R., Prisk, G. Kim, McCole, Declan F.
Format: Article
Language:English
Subjects:
13/106
13/51
631/80/79/1987
692/4020/2199
82/80
96/63
Acetaldehyde
Cell Membrane Permeability
Dextran
Epithelial Attachment - metabolism
Epithelial Attachment - physiology
Epithelial cells
Homeostasis
HT29 Cells
Humanities and Social Sciences
Humans
Immune system
Intestinal Mucosa - metabolism
Intestinal Mucosa - physiology
Intestine
Localization
Metabolites
Microgravity
Microspheres
multidisciplinary
Permeability
Science
Science (multidisciplinary)
Tight Junctions - metabolism
Tight Junctions - physiology
Virulence
Weightlessness - adverse effects
Weightlessness Simulation - adverse effects
Zonula occludens-1 protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-53862-3