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.
Highlights
A microgravity environment, such as that encountered in spaceflight, has been demonstrated to affect basic cellular function in complex biological organisms and in cells
To better understand the effects of microgravity on the functional behavior of the epithelial cells that line the intestinal tract, we examined the impact of simulated microgravity on intestinal epithelial cells cultured in a rotating wall vessel
The rotating wall vessel (RWV) generates a low shear simulated microgravity environment that enables epithelial cells to form 3-D cellular aggregates with greater in vivo-like characteristics, including tight junctions and extracellular processes such as microvilli, than conventional 2-D culture where cells are grown as flat, two-dimensional monolayers on impermeable surfaces[10,12,17,71]
Summary
A microgravity environment, such as that encountered in spaceflight, has been demonstrated to affect basic cellular function in complex biological organisms and in cells. The suppressive effects of space flight on immune function are compounded as a risk factor for long term habitation in space by evidence from Wilson et al.[28], showing increased virulence of a foodborne bacterial pathogen, Salmonella typhimurium after time spent in space This was complemented by ground-based studies demonstrating altered bacterial virulence or adherence by either bacterial or epithelial cell culture respectively in the simulated microgravity environment of the RWV17,18,29,30. We investigated if simulated microgravity, generated by culturing IECs in the RWV, altered junction formation and functional barrier properties of polarized epithelial monolayers, and if subsequent exposure to acetaldehyde induced a differential effect on barrier integrity in cells exposed to simulated microgravity conditions. Our study is the first to investigate if functional changes to epithelial cell barrier properties were sustained over time following removal from the simulated microgravity environment
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