Bifidobacteria Prevent Tunicamycin-Induced Endoplasmic Reticulum Stress and Subsequent Barrier Disruption in Human Intestinal Epithelial Caco-2 Monolayers.
Endoplasmic reticulum (ER) stress is caused by accumulation of unfolded and misfolded proteins in the ER, thereby compromising its vital cellular functions in protein production and secretion. Genome wide association studies in humans as well as experimental animal models linked ER stress in intestinal epithelial cells (IECs) with intestinal disorders including inflammatory bowel diseases. However, the mechanisms linking the outcomes of ER stress in IECs to intestinal disease have not been clarified. In this study, we investigated the impact of ER stress on intestinal epithelial barrier function using human colon carcinoma-derived Caco-2 monolayers. Tunicamycin-induced ER stress decreased the trans-epithelial electrical resistance of Caco-2 monolayers, concomitant with loss of cellular plasma membrane integrity. Epithelial barrier disruption in Caco-2 cells after ER stress was not caused by caspase- or RIPK1-dependent cell death but was accompanied by lysosomal rupture and up-regulation of the ER stress markers Grp78, sXBP1 and Chop. Interestingly, several bifidobacteria species inhibited tunicamycin-induced ER stress and thereby diminished barrier disruption in Caco-2 monolayers. Together, these results showed that ER stress compromises the epithelial barrier function of Caco-2 monolayers and demonstrate beneficial impacts of bifidobacteria on ER stress in IECs. Our results identify epithelial barrier loss as a potential link between ER stress and intestinal disease development, and suggest that bifidobacteria could exert beneficial effects on this phenomenon.
Yakult Honsha European Research Center for Microbiology ESV, Ghent, Belgium.
Takuya
T
Akiyama
Yakult Honsha European Research Center for Microbiology ESV, Ghent, Belgium.|Yakult Central Institute, Tokyo, Japan.
Kenji
K
Oishi
Yakult Honsha European Research Center for Microbiology ESV, Ghent, Belgium.|Inflammation Research Center, VIB, Ghent, Belgium.|Internal Medicine Department, Ghent University, Ghent, Belgium.
Andy
http://orcid.org/0000-0001-5012-654X
A
Wullaert
D017209:Apoptosis / Q000187:drug effects; D001644:Bifidobacterium / Q000502:physiology*; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D055106:Genome-Wide Association Study; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000633:toxicity*; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000378:metabolism
C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D014415:Tunicamycin; D051742:Transcription Factor CHOP