Transcriptional and Proteomic Analysis Revealed a Synergistic Effect of Aflatoxin M1 and Ochratoxin A Mycotoxins on the Intestinal Epithelial Integrity of Differentiated Human Caco-2 Cells

2018 ◽  
Vol 17 (9) ◽  
pp. 3128-3142 ◽  
Author(s):  
Yanan Gao ◽  
Songli Li ◽  
Xiaoyu Bao ◽  
Chaochao Luo ◽  
Huaigu Yang ◽  
...  
Toxins ◽  
2017 ◽  
Vol 10 (1) ◽  
pp. 13 ◽  
Author(s):  
Yanan Gao ◽  
Songli Li ◽  
Jiaqi Wang ◽  
Chaochao Luo ◽  
Shengguo Zhao ◽  
...  

Toxicology ◽  
2021 ◽  
pp. 152835
Author(s):  
Ziwei Wang ◽  
Yanan Gao ◽  
Xin Huang ◽  
Shengnan Huang ◽  
Xue Yang ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.


2019 ◽  
Vol 12 (4) ◽  
pp. 399-407 ◽  
Author(s):  
A. Alizadeh ◽  
P. Akbari ◽  
S. Varasteh ◽  
S. Braber ◽  
H. Malekinejad ◽  
...  

Contamination of human and animal diets with different mycotoxins have gained significant attention over the past decade. The intestinal barrier is the first site of exposure and a primary target for nutritional contaminants and hazardous substances including mycotoxins. In this study, the potential impact of ochratoxin A (OTA) on intestinal barrier integrity was highlighted using a human intestinal Caco-2 cell line. Cell viability following OTA exposure was determined by lactate dehydrogenase release and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, markers of barrier integrity, such as transepithelial electrical resistance (TEER) as well as the permeability of Lucifer Yellow (LY) and fluorescein isothiocyanate (FITC)-dextran, were assessed. Furthermore, the protein expression of different tight junction (TJ) proteins, as main constituents of barrier integrity, was evaluated by Western blot. Results show that OTA reduces TEER values in a concentration- and time-dependent manner and increase the permeability of LY through the intestinal epithelial layer, while the cell viability did not change significantly. However, the damage was not severe enough to change the permeability to larger molecules, such as FITC-dextran. OTA exposure down-regulated the expression of TJ proteins claudin-1, -3 and -4 and up-regulated the expression of zona occludens 1. The observation that OTA can disrupt the epithelial barrier is of clinical importance as it may lead to an increased passage of luminal antigens into the systemic circulation.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Banugül Barut Uyar ◽  
Nilgün Karaağaoğlu ◽  
Gözde Girgin ◽  
Aylin Gürbay ◽  
Ergun Karaağaoğlu

2009 ◽  
Vol 2 (4) ◽  
pp. 451-459 ◽  
Author(s):  
G. Bakker ◽  
E. Sizoo ◽  
A. Jekel ◽  
D.P. Pereboom-de Fauw ◽  
R. Schothorst ◽  
...  

In 2006, a duplicate diet study of children's food was carried out in the Netherlands. Parents or guardians of 123 children collected duplicates of the 24-hour diets. Levels of aflatoxin M1, aflatoxin B1, ochratoxin A, trichothecenes and fumonisins were determined. Aflatoxin M1 was detectable in 10% of the samples, with all toxin levels below the limit of quantification. Aflatoxin B1 could be detected in 80% of the samples, while in 47% of all samples aflatoxin B1 was quantifiable. Ochratoxin A could be quantified in all samples. Deoxynivalenol was quantified in almost every sample, while T-2 and HT-2 toxins could only be quantified in 3.2% and 6.4% of the samples respectively. 15-acetyldeoxynivalenol was detected in 1.6% of the samples. Fumonisin B1 was detected in 28% of the samples and fumonisin B2 in a quarter of merely those samples where fumonisin B1 was detected. In 20% of the samples fumonisin B1 could be quantified and in a quarter of those samples fumonisin B2 could be quantified too. The analytical results were used to estimate levels of daily intake. Only the mean daily intake levels for aflatoxin B1, ochratoxin A, deoxynivalenol and fumonisins B1 and B2 could reliably be estimated. The values were 0.1, 4.1, 291 and 28 ng/kg bw/day respectively, all are well below the corresponding tolerable daily intakes. For aflatoxin B1 a tolerable intake does not exist, but the intake value for this mycotoxin was very low if compared to the value that would result from the intake of food, if it was contaminated with aflatoxin B1 at the EU regulatory limit, specified for baby food. The mean daily intakes of the mycotoxins determined in children's food in the Netherlands are low and implicate that there is no health risk for children due to exposure from the studied mycotoxins.


Toxicon ◽  
2020 ◽  
Vol 187 ◽  
pp. 209-213
Author(s):  
Fateme Samiee ◽  
Ava Kharazi ◽  
Jomana Elaridi ◽  
Masoumeh Taravati Javad ◽  
Mostafa Leili

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