Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

Cui, Wanpeng; Li, L X; Sun, Chunyan; Wen, Yuanyuan; Zhou, Ying; Dong, Y L; Liu, P

doi:10.1590/s0100-879x2010007500020

Cited by 71 publications

(54 citation statements)

References 40 publications

(49 reference statements)

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“…PON2 KD did not result in significant changes in sucrase, a microvillar hydrolase considered the most reliable indicator of intestinal cell differentiation in vitro (40), or in villin, the major cytoskeletal protein of the brush border in epithelial cells of the digestive tract (5,26). Similarly, no differences between Mock and PON2 KD cells were observed in expression of occludin, a tetra-transmembrane protein that, with other structural components, seals the space between adjacent cells by forming tight junctions (9). These junctional complexes are well known to function not only as a control for the paracellular diffusion of ions and certain molecules, but also as vital structures able to control signal transduction and cell integrity (1).…”

Section: Discussionmentioning

confidence: 85%

“…As assessed by Trypan blue exclusion, cell viability was not affected (data not shown). Furthermore, under these normal conditions, the gene and protein expression of villin was analyzed as a marker of cell differentiation and that of occludin as a marker of tight junctions and mucosal barrier function (9), and no significant differences were observed between Mock and PON2 KD cells (Fig. 2) 2 ) were not different between PON2 KD and Mock cells, respectively.…”

Section: Validation Of Pon2 Kd In Caco-2/15 Cellsmentioning

confidence: 96%

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Antioxidative properties of paraoxonase 2 in intestinal epithelial cells

Précourt

Marcil

Ntimbane

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Paraoxonase (PON) family members seem central to a wide variety of human illnesses, but appreciation of their antioxidative function in the gastrointestinal tract is in its infancy. The major objective of the present work is to highlight the role of the ubiquitously expressed PON2 in the small intestine. With use of pLKO lentiviral vector containing short hairpin RNA (shRNA) lentivirus, PON2 expression was knocked down in intestinal Caco-2/15 cells, where antioxidative status, lipid peroxidation, and degree of inflammation were evaluated. As a consequence of PON2 inactivation in the epithelial cells, we observed 1) imbalanced primary and secondary antioxidative responses, characterized by increased superoxide dismutases and decreased catalase, 2) high concentrations of H2O2 and malondialdehyde, along with low glutathione-to-glutathione disulfide ratio, 3) upregulation of TNF-α, IL-6, and monocyte chemoattractant protein-1 gene expression after induction of oxidative stress, and 4) raised level of the activation of transcription factor NF-κB, which was likely implicated in exacerbation of the inflammatory activation. These results suggest that PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells.

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Section: Discussionmentioning

confidence: 85%

Section: Validation Of Pon2 Kd In Caco-2/15 Cellsmentioning

confidence: 96%

Antioxidative properties of paraoxonase 2 in intestinal epithelial cells

Précourt

Marcil

Ntimbane

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…However, an additional study reported that the levels of claudin-1 and claudin-4 did not markedly change, while the downregulation of JAM was observed in a human airway epithelial cell line (9). Furthermore, a previous study reported that TNF-α causes the decreased expression of active occludin molecules, which leads to the disruption of TJ structure in Caco-2 cells (8). However, an additional study reported that TNF-α causes an increase in the levels of active occludin in human airway epithelial cells, which was hypothesized to have occurred due the presence of a leaky junction (8,9).…”

Section: Introductionmentioning

confidence: 93%

“…Tumor necrosis factor (TNF)-α has been shown to reduce claudin expression in a variety of tissues (6)(7)(8). However, the mechanism underlying this effect remains unclear with different studies reporting variable results.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, a previous study reported that TNF-α causes the decreased expression of active occludin molecules, which leads to the disruption of TJ structure in Caco-2 cells (8). However, an additional study reported that TNF-α causes an increase in the levels of active occludin in human airway epithelial cells, which was hypothesized to have occurred due the presence of a leaky junction (8,9). Thus, TNF-α antagonism is hypothesized to improve epithelial barrier integrity.…”

Section: Introductionmentioning

confidence: 99%

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Vascular endothelial growth factor antagonism restores epithelial barrier dysfunction via affecting zonula occludens proteins

Yüksel

Yılmaz

Karaman

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Epithelial barrier dysfunction is important in the pathogenesis of asthma and allergic responses, and is therefore a therapeutic target. The aim of the present study was to investigate the effects of dexamethasone, a classic therapeutic agent, an anti-tumor necrosis factor agent (etanercept), which is used to treat difficult cases of asthma, and an anti-vascular endothelial growth factor (VEGF) agent (bevacizumab), which is an angiogenesis inhibitor, on zonula occludens (ZO) proteins in an experimental asthma model. The experimental model of asthma was developed using intraperitoneal (IP) and inhaled administration of ovalbumin in 38 BALB/c mice, which were divided into four groups. The control group (n=6) did not receive any treatment, while the four remaining groups (n=8 per group) received an IP injection of saline, etanercept, bevacizumab or dexamethasone, respectively. Occludin, claudin and junctional adhesion molecule (JAM) were immunohistochemically stained in the left middle lobe samples using an indirect avidin-peroxidase method, after which the staining was semiquantified with H-scores. Statistically significant differences were observed in the occludin, claudin and JAM H-scores among the four groups (P<0.001). In the untreated asthma, etanercept, bevacizumab and dexamethasone groups, the median H-scores for occludin were 93, 177, 280 and 198, respectively, while the H-scores for claudin were 82, 193.5, 274 and 202.5, respectively, and the median H-scores for JAM were 130, 210, 288 and 210, respectively. Pairwise comparisons revealed that all three ZO protein H-scores were significantly lower in the saline group when compared with each treatment group. However, the H-scores of the ZO proteins were not significantly different between the etanercept and dexamethasone groups. Furthermore, the bevacizumab group exhibited higher H-scores for all the proteins compared with the dexamethasone group. Therefore, antagonism of VEGF with bevacizumab restores the epithelial barrier to a greater extent when compared with dexamethasone treatment. This result may be promising for the development of novel therapeutic agents. IntroductionEpithelial tissue, in addition to forming a physical barrier to external stimuli, plays a major role in the regulation of the adaptive immune response. The physical barrier function of the epithelium is attained via cell-cell interactions and via impermeable tight junctions (TJs) that are located subapically (1).Claudins, occludin and junctional adhesion molecules (JAMs) are major constituent proteins of TJs. The claudin family comprises 24 members, and determines the TJ charge selectivity and the location of the paracellular space (2). In addition, human fetal lung cells have been shown to use differential claudin expression to regulate TJ permeability (3). Occludin is an additional protein that is important in barrier formation and regulation (2). JAM-1, which is a member of the immunoglobulin superfamily, has been shown to interact with zonula occludens (ZO)-1, occludin and...

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