Mechanisms of deoxynivalenol-induced endocytosis and degradation of tight junction proteins in jejunal IPEC-J2 cells involve selective activation of the MAPK pathways

Li, Enkai; Horn, Nathan; Ajuwon, Kolapo M.

doi:10.1007/s00204-021-03044-w

Cited by 42 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 30 Furthermore, p38 activation plays an important role in regulating the flagellin-induced innate immune response in airway epithelia during infection with the human pathogen Pseudomonas aeruginosa. 31 Interestingly, in line with our Western blot results, Li 32 recently found that deoxynivalenol accelerates the endocytosis and degradation of tight junction proteins and that this process is regulated by the activation of p38 MAPK signaling pathways by a c-Jun-N-terminal kinase (JNK). Lithium enhances post-stroke blood-brain barrier integrity by regulating tight junctions and has also been identified as a key regulator of the prosurvival MAPK/ERK1/2 pathway.…”

Section: Resultssupporting

confidence: 78%

The Analysis of the Ubiquitylomic Responses to Streptococcus agalactiae Infection in Bovine Mammary Gland Epithelial Cells

Tong¹,

Ji²,

Zhang³

et al. 2022

JIR

View full text Add to dashboard Cite

Streptococcus agalactiae is one of the primary pathogens responsible for subclinical mastitis, a significant economic burden for dairy farms. An essential component of the immune response to infection is ubiquitination, which plays important roles in the complex interactions between the pathogen and host. Materials and Methods:In the present study, quantitative ubiquitylomics was performed to profile changes in the global ubiquitinome of bovine mammary gland epithelial cells (BMECs) infected with S. agalactiae. Results: The most notable changes in the BMEC ubiquitinome were related to the adherens junction, ribosome, and tight junction pathways. Ubiquitination of CTNNB1, EGFR, ITGB1, CTNNA1, CTNNA2, CDH1, YES1, and SLC9A3R1 appears to be fundamental for regulating multiple cellular processes in BMECs in response to S. agalactiae infection. In addition, broad ubiquitination of various effectors and outer membrane proteins was observed. Ubiquitinated proteins in S. agalactiae-infected BMECs were associated with regulating cell junctions in the host, with potential implications for susceptibility to infection. Conclusion:The preliminary findings suggest that extensive ubiquitination of CTNNB1, CDH1 and SLC9A3R1 and proteins closely related to cell junctions might play an important role in mastitis progression in dairy cows. The results provide evidence that ubiquitin modification of certain proteins in S. agalactiae-infected BMECs could be a promising therapeutic strategy for reducing mammary gland injury and mastitis.

show abstract

Section: Resultssupporting

confidence: 78%

The Analysis of the Ubiquitylomic Responses to Streptococcus agalactiae Infection in Bovine Mammary Gland Epithelial Cells

Tong¹,

Ji²,

Zhang³

et al. 2022

JIR

View full text Add to dashboard Cite

show abstract

“…In our experimental setup, we observed both AOH and DON to reduce ZO-1 immunofluorescence signals (Figure 6). Even if data on AOH are limited, a similar concentration of DON (2 µM) was suggested to induce epithelial barrier disruption by the degradation of tight junction proteins via p38 MAPK and JNK signaling (93), p38 MAPK being recognized as one pathway triggered by low doses of DON contributing to its pro-inflammatory effects (94). Combinatory exposure to Uro A and AOH led to enhanced ZO-1 immunolocalization (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

Combinatory Exposure to Urolithin A, Alternariol, and Deoxynivalenol Affects Colon Cancer Metabolism and Epithelial Barrier Integrity in vitro

et al. 2022

View full text Add to dashboard Cite

The human gastrointestinal tract is an important site of nutrient absorption and a crucial barrier against xenobiotics. It regularly faces “chemical cocktails” composed of food constituents, their human and microbial metabolites, and foodborne contaminants, such as mycotoxins. Hence, the colonic epithelium adapts to dietary molecules tuning its immune response, structural integrity, and metabolism to maintain intestinal homeostasis. While gut microbiota metabolites of berry ellagitannins, such as urolithin A (Uro A) might contribute to physiological epithelial barrier integrity, foodborne co-contaminating mycotoxins like alternariol (AOH) and deoxynivalenol (DON) could hamper epithelial function. Hence, we investigated the response of differentiated Caco-2 cells (clone C2BBe1) in vitro to the three compounds alone or in binary mixtures. In virtue of the possible interactions of Uro A, AOH, and DON with the aryl hydrocarbon receptor (AhR) pathway, potential effects on phase-I-metabolism enzymes and epithelial structural integrity were taken as endpoints for the evaluation. Finally, Liquid chromatography tandem mass spectrometry measurements elucidated the absorption, secretion, and metabolic capacity of the cells under single and combinatory exposure scenarios. Uro A and AOH as single compounds, and as a binary mixture, were capable to induce CYP1A1/1A2/1B1 enzymes triggered by the AhR pathway. In light of its ribosome inhibiting capacity, the trichothecene suppressed the effects of both dibenzo-α-pyrones. In turn, cellular responsiveness to Uro A and AOH could be sustained when co-exposed to DON-3-sulfate, instead of DON. Colonic epithelial structural integrity was rather maintained after incubation with Uro A and AOH: this was reinforced in the combinatory exposure scenario and disrupted by DON, an effect, opposed in combination. Passage through the cells as well as the metabolism of Uro A and AOH were rather influenced by co-exposure to DON, than by interaction with each other. Therefore, we conclude that although single foodborne bioactive substances individually could either support or disrupt the epithelial structure and metabolic capacity of colon cancer, exposure to chemical mixtures changes the experimental outcome and calls for the need of combinatory investigations for proper risk assessment.

show abstract

“…Resveratrol, a polyphenolic compound abundant in grape skin, was able to counteract decreases in TEER and elevate paracellular permeability. Furthermore, integrity was promoted by an increased expression of CLDN-4 via mitogen-activated protein kinase-dependent (MAPK) pathways in IPEC-J2 cells challenged with mycotoxins deoxynivalenol (DON) [ 57 , 58 ]. As resveratrol has an inhibitory effect on c-Jun-N-terminal kinase (JNK), findings revealed that reduction of endocytosis and degradation of CLDN-4 and TJ associated gene ZO-1 by DON further seems to be regulated by JNK [ 58 ].…”

Section: Intestinal Porcine Epithelial Cell Linesmentioning

confidence: 99%

“…Furthermore, integrity was promoted by an increased expression of CLDN-4 via mitogen-activated protein kinase-dependent (MAPK) pathways in IPEC-J2 cells challenged with mycotoxins deoxynivalenol (DON) [ 57 , 58 ]. As resveratrol has an inhibitory effect on c-Jun-N-terminal kinase (JNK), findings revealed that reduction of endocytosis and degradation of CLDN-4 and TJ associated gene ZO-1 by DON further seems to be regulated by JNK [ 58 ]. In a model using a mixture of the mycotoxins DON and fusariotoxin T 2 (T2) to impair barrier function, rosmarinic acid showed the ability to restore TEER and to promote distribution of TJ protein CLDN-1.…”

Section: Intestinal Porcine Epithelial Cell Linesmentioning

confidence: 99%

Porcine and Chicken Intestinal Epithelial Cell Models for Screening Phytogenic Feed Additives—Chances and Limitations in Use as Alternatives to Feeding Trials

et al. 2022

View full text Add to dashboard Cite

Numerous bioactive plant additives have shown various positive effects in pigs and chickens. The demand for feed additives of natural origin has increased rapidly in recent years to support the health of farm animals and thus minimize the need for antibiotics and other drugs. Although only in vivo experiments can fully represent their effect on the organism, the establishment of reliable in vitro methods is becoming increasingly important in the goal of reducing the use of animals in experiments. The use of cell models requires strict control of the experimental conditions so that reliability and reproducibility can be achieved. In particular, the intestinal porcine epithelial cell line IPEC-J2 represents a promising model for the development of new additives. It offers the possibility to investigate antioxidative, antimicrobial, anti- or pro-proliferative and antiviral effects. However, the use of IPEC-J2 is limited due to its purely epithelial origin and some differences in its morphology and functionality compared to the in vivo situation. With regard to chickens, the development of a reliable intestinal epithelial cell model has attracted the attention of researchers in recent years. Although a promising model was presented lately, further studies are needed to enable the standardized use of a chicken cell line for testing phytogenic feed additives. Finally, co-cultivation of the currently available cell lines with other cell lines and the development of organoids will open up further application possibilities. Special emphasis was given to the IPEC-J2 cell model. Therefore, all publications that investigated plant derived compounds in this cell line were considered. The section on chicken cell lines is based on publications describing the development of chicken intestinal epithelial cell models.

show abstract

Mechanisms of deoxynivalenol-induced endocytosis and degradation of tight junction proteins in jejunal IPEC-J2 cells involve selective activation of the MAPK pathways

Cited by 42 publications

References 36 publications

The Analysis of the Ubiquitylomic Responses to Streptococcus agalactiae Infection in Bovine Mammary Gland Epithelial Cells

The Analysis of the Ubiquitylomic Responses to Streptococcus agalactiae Infection in Bovine Mammary Gland Epithelial Cells

Combinatory Exposure to Urolithin A, Alternariol, and Deoxynivalenol Affects Colon Cancer Metabolism and Epithelial Barrier Integrity in vitro

Porcine and Chicken Intestinal Epithelial Cell Models for Screening Phytogenic Feed Additives—Chances and Limitations in Use as Alternatives to Feeding Trials

Contact Info

Product

Resources

About