Impact of deoxynivalenol and kaempferol on expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation

Wang, Xiaojie; Li, Li; Zhang, Genyi

doi:10.1039/c9ra06222j

Cited by 13 publications

(19 citation statements)

References 38 publications

(41 reference statements)

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“…Exposure of 21-day cultured Caco-2 cell layers to 2.5 μM DON and lower concentrations did neither alter the cell layer barrier properties nor did it reduce the cell viability, which was in agreement with previous studies on differentiated Caco-2 cell layers (Bony et al 2006 ; Wang et al 2019 ). However pre-exposure to 2 μM DON decreased the amount of TCA transported across the Caco-2 cell layers.…”

Section: Discussionsupporting

confidence: 92%

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells

et al. 2022

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Conjugated bile acids are synthesized in liver and subsequently secreted into the intestinal lumen from which they are actively reabsorbed and transported back to liver. The efficient enterohepatic circulation of conjugated bile acids is important to maintain homeostasis. The mycotoxin deoxynivalenol (DON) is a fungal secondary metabolite that contaminates cereal food. Upon human exposure, it can cause intestinal dysfunction. We explored the effects of DON exposure on the intestinal absorption of conjugated bile acids and the expression of bile acid transporters using an in vitro model based on Caco-2 cell layers grown in transwells. Our study shows that the transport rate of taurocholic acid (TCA) is decreased after 48-h pre-exposure of the Caco-2 cells to 2 µM DON, which is a realistic intestinal DON concentration. Exposure to DON downregulates expression of the genes coding for the apical sodium-dependent bile acid transporter (ASBT), the ileal bile acid-binding protein (IBABP) and the organic solute transporter α (OSTα), and it counteracts the agonist activity of Farnesoid X receptor (FXR) agonist GW4064 on these genes. In addition, the transport of ten taurine or glycine-conjugated bile acids in a physiological relevant mixture by the intestinal Caco-2 cell layers was decreased after pre-exposure of the cells to DON, pointing at a potential for DON-mediated accumulation of the conjugated bile acids at the intestinal luminal side. Together the results reveal that DON inhibits intestinal bile acid reabsorption by reducing the expression of bile acid transporters thereby affecting bile acid intestinal kinetics, leading to bile acid malabsorption in the intestine. Our study provides new insights into the hazards of DON exposure.

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Section: Discussionsupporting

confidence: 92%

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells

et al. 2022

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“…5,6) Although α-defensin 5 is not present in normal large intestines, 7) Caco-2 cells, which are gastrointestinal model cells, express α-defensin 5 and alkaline phosphatase (ALP), a differ-entiation marker for cells similar to small intestinal cells; the ALP activity fluctuates with the number of culture days. [8][9][10] Therefore, we focused on whether Caco-2 cells could be used as a model for evaluating α-defensin 5 secretion. To this end, we examined the effect of cell differentiation in Caco-2 cells on α-defensin 5 secretory ability and the mRNA levels of various cytokines in an attempt to determine the appropriate conditions for using Caco-2 cells as a model for measuring α-defensin 5 secretion.…”

Section: Introductionmentioning

confidence: 99%

Analysis of α-Defensin 5 Secretion in Differentiated Caco-2 Cells: Comparison of Cell Bank Origin

Yasuda

Kobayashi

Kubota

et al. 2021

Biological & Pharmaceutical Bulletin

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α-Defensin 5 has a particularly broad antibacterial spectrum; it eliminates pathogenic microorganisms and regulates intestinal flora. Although Caco-2 cells are similar to small intestinal cells, it is unclear whether they secrete α-defensin 5. Therefore, we investigated whether Caco-2 cells secrete α-defensin 5 and determined the secretion mechanism using cells from three cell banks (ATCC, DSMZ, and RIKEN). The Caco-2 cell proliferation rate increased with the number of culture days, irrespective of cell bank origin. On the other hand, the alkaline phosphatase activity, which affects cell differentiation and the mRNA levels of several cytokines, such as interleukin 8 (IL-8), IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and IL-2, in the Caco-2 cells fluctuated with the number of culture days, and differed for each cell bank. α-Defensin 5 secretion was detected in all three cell bank Caco-2 cells; particularly, the ATCC Caco-2 cells grew linearly depending on the cell culture day as well as the levels of IL-8 and TNF-α mRNA. This suggested that α-defensin 5 secretion in the ATCC Caco-2 cells was associated with fluctuations in the mRNA levels of various cytokines, such as IL-8 and TNF-α. In conclusion, Caco-2 cells may be a simple model for screening health food components and drugs that affect α-defensin 5 secretion.

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“…Besides live pathogens, some secreted bacterial toxins such as cereulide (CER) from B. cereus can influence tight junction protein expression, although the final direction of their impact is not yet completely understood, as contrasting results of both increased and decreased expressions have been collected hitherto (X. Wang et al, 2019). Finally, microcystins from cyanobacteria can affect the barrier integrity of intestinal epithelium by decreasing transepithelial electrical resistance, which is the measurement of the resistance of an epithelial monolayer, and expressing occludin enzyme and zonula occludens (ZO)-1 protein (J.-X.…”

Section: Foodborne Pathogens Possibly Facilitate Paracellular Transpo...mentioning

confidence: 99%

Foodborne pathogens in the plastisphere: Can microplastics in the food chain threaten microbial food safety?

Tavelli

Callens²,

Grootaert³

et al. 2022

Trends in Food Science & Technology

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Impact of deoxynivalenol and kaempferol on expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation

Abstract: The expression of tight junction proteins in human epithelial colorectal adenocarcinoma (Caco-2) cells was investigated after treatment by the mycotoxin of deoxynivalenol and phenolic compound of kaempferol in different stages of proliferation and differentiation.

Cited by 13 publications

References 38 publications

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells

Exposure to the mycotoxin deoxynivalenol reduces the transport of conjugated bile acids by intestinal Caco-2 cells

Analysis of α-Defensin 5 Secretion in Differentiated Caco-2 Cells: Comparison of Cell Bank Origin

Foodborne pathogens in the plastisphere: Can microplastics in the food chain threaten microbial food safety?

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