Abstract:Intestinal epithelial barrier is affected by multiple factors, such as tumour necrosis factor-α (TNF-α). Plasma concentration of TNF-α is higher in patients with Crohn’s disease (CD) than healthy controls (HC) and correlates positively with disease activity. This study aimed to determine the effect of plasma from active, inactive CD patients on intestinal barrier function and to investigate the underlying mechanism. Plasma samples were collected from CD patients and HC. 3D Caco-2 cysts were treated with plasma… Show more
“…On the other hand alteration in permeability may also activate immune cells leading to infection and inflammation [23]. Moreover, cytokines such as intestinal tumor necrosis factor α (TNF-α) are usually elevated during gastrointestinal inflammation [24]. Fig.…”
Background
Silver ions from silver nanoparticles (AgNP) or AgNPs themselves itself that are ingested from consumer health care products or indirectly from absorbed food contact material can interact with the gastrointestinal tract (GIT). The permeability of the GIT is strictly regulated to maintain barrier function and proper nutrient absorption. The single layer intestinal epithelium adheres and communicates actively to neighboring cells and the extracellular matrix through different cell junctions. In the current study, we hypothesized that oral exposure to AgNPs may alter the intestinal permeability and expression of genes controlling cell junctions. Changes in cell junction gene expression in the ileum of male and female rats administered different sizes of AgNP for 13-weeks were assessed using qPCR.
Results
The results of this study indicate that AgNPs have an altering effect on cell junctions that are known to dictate intestinal permeability. mRNA expression of genes representing tight junction (
Cldn1, Cldn5, Cldn6
,
Cldn10
and
Pecam1
), focal adhesion (
Cav1, Cav2
, and
Itgb2
), adherens junction (
Pvrl1, Notch1
, and
Notch2
), and hemidesmosome (
Dst
) groups were upregulated significantly in females treated with 10 nm AgNP, while no change or downregulation of same genes was detected in male animals. In addition, a higher concentration of pro-inflammatory cytokine, TNF-α, was noticed in AgNP-treated female animals as compared to controls.
Conclusions
This study proposes that interaction of silver with GIT could potentially initiate an inflammatory process that could lead to changes in the gastrointestinal permeability and/or nutrient deficiencies in sex-specific manner. Fully understanding the mechanistic consequences of oral AgNP exposure may lead to stricter regulation for the commercial usage of AgNPs and/or improved clinical therapy in the future.
“…On the other hand alteration in permeability may also activate immune cells leading to infection and inflammation [23]. Moreover, cytokines such as intestinal tumor necrosis factor α (TNF-α) are usually elevated during gastrointestinal inflammation [24]. Fig.…”
Background
Silver ions from silver nanoparticles (AgNP) or AgNPs themselves itself that are ingested from consumer health care products or indirectly from absorbed food contact material can interact with the gastrointestinal tract (GIT). The permeability of the GIT is strictly regulated to maintain barrier function and proper nutrient absorption. The single layer intestinal epithelium adheres and communicates actively to neighboring cells and the extracellular matrix through different cell junctions. In the current study, we hypothesized that oral exposure to AgNPs may alter the intestinal permeability and expression of genes controlling cell junctions. Changes in cell junction gene expression in the ileum of male and female rats administered different sizes of AgNP for 13-weeks were assessed using qPCR.
Results
The results of this study indicate that AgNPs have an altering effect on cell junctions that are known to dictate intestinal permeability. mRNA expression of genes representing tight junction (
Cldn1, Cldn5, Cldn6
,
Cldn10
and
Pecam1
), focal adhesion (
Cav1, Cav2
, and
Itgb2
), adherens junction (
Pvrl1, Notch1
, and
Notch2
), and hemidesmosome (
Dst
) groups were upregulated significantly in females treated with 10 nm AgNP, while no change or downregulation of same genes was detected in male animals. In addition, a higher concentration of pro-inflammatory cytokine, TNF-α, was noticed in AgNP-treated female animals as compared to controls.
Conclusions
This study proposes that interaction of silver with GIT could potentially initiate an inflammatory process that could lead to changes in the gastrointestinal permeability and/or nutrient deficiencies in sex-specific manner. Fully understanding the mechanistic consequences of oral AgNP exposure may lead to stricter regulation for the commercial usage of AgNPs and/or improved clinical therapy in the future.
“…Despite ardent research efforts in the intestine due its diverse functions in the human body [115][116][117][118], we still lack the mechanistic understanding of many aspects of the intestinal environment. While animal models enable systemic analyses of the intestinal environment, it is hard to investigate the contribution of each component in the intestine to the observed responses.…”
Section: Current In Vitro Models Of the Intestinementioning
confidence: 99%
“…The previously developed gut-on-chips incorporated the intestinal endothelium in the lower channel and revealed that the endothelium is important for the maintenance of the intestinal barrier and the production of the mucus [116,127]. Especially in disease conditions, the contents in the plasma transported by the intestinal blood vessels could affect intestinal epithelium functions [118]. However, these previous models failed to mimic the physiological structures of intestinal microcirculation.…”
The human circulatory system is divided into two complementary and different systems, the cardiovascular and the lymphatic system. The cardiovascular system is mainly concerned with providing nutrients to the body via blood and transporting wastes away from the tissues to be released from the body. The lymphatic system focuses on the transport of fluid, cells, and lipid from interstitial tissue spaces to lymph nodes and, ultimately, to the cardiovascular system, as well as helps coordinate interstitial fluid and lipid homeostasis and immune responses. In addition to having distinct structures from each other, each system also has organ-specific variations throughout the body and both systems play important roles in maintaining homeostasis. Dysfunction of either system leads to devastating and potentially fatal diseases, warranting accurate models of both blood and lymphatic vessels for better studies. As these models also require physiological flow (luminal and interstitial), extracellular matrix conditions, dimensionality, chemotactic biochemical gradient, and stiffness, to better reflect in vivo, three dimensional (3D) microfluidic (on-a-chip) devices are promising platforms to model human physiology and pathology. In this review, we discuss the heterogeneity of both blood and lymphatic vessels, as well as current in vitro models. We, then, explore the organ-specific features of each system with examples in the gut and the brain and the implications of dysfunction of either vasculature in these organs. We close the review with discussions on current in vitro models for specific diseases with an emphasis on on-chip techniques.
“…As the MAPK pathway could affect tight junctions and cause dysfunction of the intestinal barrier 23,25,26 , we further examined whether PXR could regulate MAPK pathway signaling. After Caco-2 cells were treated with LPS at 5 μg/ml for 30 min, we observed increased phosphorylation of Erk and p38 and a notable increase in phospho-JNK levels (Fig.…”
Section: Pxr Could Inhibit the Phosphorylation Of Jnkmentioning
Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor ( PXR ) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.
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