scholarly journals Neonatal Hyperoxia Downregulates Claudin-4, Occludin, and ZO-1 Expression in Rat Kidney Accompanied by Impaired Proximal Tubular Development

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Xuewen Xu ◽  
Xinyue Zhang ◽  
Linlin Gao ◽  
Chunfeng Liu ◽  
Kai You
Keyword(s):  
Tight Junction ◽  
Renal Injury ◽  
Rat Kidney ◽  
Proximal Tubules ◽  
Inflammatory Factors ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Neonatal Hyperoxia ◽  
Junction Proteins

Hyperoxia is essential to manage in preterm infants but causes injury to immature kidney. Previous study indicates that hyperoxia causes oxidative damage to neonatal kidney and impairs renal development. However, the underlying mechanisms by which neonatal hyperoxia effects on immature kidney still need to be elucidated. Tight junction, among which the representative proteins are claudin-4, occludin, and ZO-1, plays a crucial role in nephrogenesis and maintaining renal function. Inflammatory cytokines are involved in the pleiotropic regulation of tight junction proteins. Here, we investigated how neonatal hyperoxia affected the expression of key tight junction proteins and inflammatory factors (IL-6 and TNF-α) in the developing rat kidneys and elucidated their correlation with renal injury. We found claudin-4, occludin, and zonula occludens-1 (ZO-1) expression in proximal tubules was significantly downregulated after neonatal hyperoxia. The expression of these tight junction proteins was positively correlated with that of IL-6 and TNF-α, while claudin-4 expression was positively correlated with injury score of proximal tubules in mature kidneys. These findings indicated that impaired expression of tight junction proteins in kidney might be a potential mechanism of hyperoxia-induced nephrogenic disorders. It provides new insights to further study oxidative renal injury and development disorders and will be helpful for seeking potential therapeutics for hyperoxia-induced renal injury in the future.

Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells

2013 ◽  
Vol 304 (11) ◽  
pp. G970-G979 ◽  
Author(s):  
Andreas Fischer ◽  
Markus Gluth ◽  
Ulrich-Frank Pape ◽  
Bertram Wiedenmann ◽  
Franz Theuring ◽  
...  
Keyword(s):  
Tight Junction ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Model Systems ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Junction Proteins

Intestinal barrier dysfunction is pivotal in the etiology of inflammatory bowel diseases. Combined clinical and endoscopic remission (“mucosal healing”) in patients who received anti-TNF-α therapies suggests restitution of the intestinal barrier, but the mechanisms involved are largely unknown. We therefore investigated the impact of the anti-TNF-α antibody adalimumab on barrier function in two in vitro models. Combined stimulation of Caco-2 and T-84 cells with interferon-γ and TNF-α resulted in a significant decrease of transepithelial electrical resistance (TEER) within 6 h that was prevented by adalimumab in concentrations down to 100 ng/ml. Adalimumab furthermore antagonized the appearance of irregular membrane undulations and prevented internalization of tight junction proteins upon cytokine exposure. In addition, TNF-α induced a downregulation of claudin-1, claudin-2, claudin-4, and occludin as well as activation of phosphatidylinositol 3-kinase signaling in T-84 but not Caco-2 cells, which was reversed by adalimumab. At the signaling level, adalimumab prevented increased phosphorylation of myosin light chain as well as activation of p38 MAPK and NF-κB accompanying the decline in TEER in both model systems. Pharmacological inhibition of NF-κB signaling partially prevented the TNF-α-induced TEER loss, whereas inhibition of p38 worsened barrier dysfunction in Caco-2 but not T-84 cells. Taken together, these data demonstrate that adalimumab prevents barrier dysfunction induced by TNF-α both functionally and structurally as well as at the level of signal transduction. Barrier protection might therefore constitute a novel mechanism how anti-TNF-α therapy contributes to epithelial restitution and tissue repair in inflammatory bowel diseases.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

Alanyl-glutamine ameliorates lipopolysaccharide-induced inflammation and barrier function injury in bovine jejunum epithelial cells

2019 ◽  
Vol 97 (6) ◽  
pp. 670-680 ◽  
Author(s):  
Xianglun Zhang ◽  
Xiuwen Tan ◽  
Yifan Liu ◽  
Wei You ◽  
Guifen Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Tight Junction ◽  
Cell Viability ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Factors ◽  
Tight Junction Proteins ◽  
Mrna And Protein Expression ◽  
Junction Proteins

The aim of this study was to investigate the effects of alanyl-glutamine (Ala-Gln) on the regulation of lipopolysaccharide (LPS)-induced inflammation and barrier function in bovine jejunum epithelial cells (BJECs). BJECs were exposed (or not) to 1 μg/mL LPS for 24 h to generate a pro-inflammatory model. The cells were then treated with different concentrations of Ala-Gln (0.25, 0.5, 1.0, 2.0, or 4.0 mmol/L) to detect any regulatory effects on the inflammation and barrier function of BJECs. LPS decreased cell viability and enhanced the production of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8. LPS induced inflammation and damaged the barrier function of BJECs, as evidenced by up-regulated mRNA and protein expression of inflammatory factors and down-regulated expression of tight junction proteins. Conversely, Ala-Gln rescued the decrease in cell viability and prevented the accumulation of ILs after LPS exposure by reducing the mRNA and protein expression levels of inflammatory factors. In addition, Ala-Gln induced the mRNA and protein expression of multiple tight junction proteins, and thus reconstituted the barrier function of BJECs. In conclusion, Ala-Gln attenuates injury from inflammation and repairs damaged intestinal barrier induced with LPS, suggesting its potential as a therapeutic agent against intestinal inflammation in mammals.

Secreted bioactive factors fromBifidobacterium infantisenhance epithelial cell barrier function

2008 ◽  
Vol 295 (5) ◽  
pp. G1025-G1034 ◽  
Author(s):  
Julia B. Ewaschuk ◽  
Hugo Diaz ◽  
Liisa Meddings ◽  
Brendan Diederichs ◽  
Andrea Dmytrash ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Tight Junction ◽  
Cell Permeability ◽  
Tight Junction Proteins ◽  
Gut Permeability ◽  
Tnf Α ◽  
Ifn Γ ◽  
The Impact ◽  
Deficient Mice ◽  
Junction Proteins

Live probiotic bacteria are effective in reducing gut permeability and inflammation. We have previously shown that probiotics release peptide bioactive factors that modulate epithelial resistance in vitro. The objectives of this study were to determine the impact of factors released from Bifidobacteria infantis on intestinal epithelial cell permeability and tight junction proteins and to assess whether these factors retain their bioactivity when administered to IL-10-deficient mice. B. infantis conditioned medium (BiCM) was applied to T84 human epithelial cells in the presence and absence of TNF-α and IFN-γ. Transepithelial resistance (TER), tight junction proteins [claudins 1, 2, 3, and 4, zonula occludens (ZO)-1, and occludin] and MAP kinase activity (p38 and ERK) were examined. Acute effects of BiCM on intestinal permeability were assessed in colons from IL-10-deficient mice in Ussing chambers. A separate group of IL-1-deficient mice was treated with BiCM for 4 wk and then assessed for intestinal histological injury, cytokine levels, epithelial permeability, and immune response to bacterial antigens. In T84 cells, BiCM increased TER, decreased claudin-2, and increased ZO-1 and occludin expression. This was associated with enhanced levels of phospho-ERK and decreased levels of phospho-p38. BiCM prevented TNF-α- and IFN-γ-induced drops in TER and rearrangement of tight junction proteins. Inhibition of ERK prevented the BiCM-induced increase in TER and attenuated the protection from TNF-α and IFN-γ. Oral BiCM administration acutely reduced colonic permeability in mice whereas long-term BiCM treatment in IL-10-deficient mice attenuated inflammation, normalized colonic permeability, and decreased colonic and splenic IFN-γ secretion. In conclusion, peptide bioactive factors from B. infantis retain their biological activity in vivo and are effective in normalizing gut permeability and improving disease in an animal model of colitis. The effects of BiCM are mediated in part by changes in MAP kinases and tight junction proteins.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Background: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals Lactobacillus casei Zhang Counteracts Blood-Milk Barrier Disruption and Moderates the Inflammatory Response in Escherichia coli-Induced Mastitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuhui Zheng ◽  
Gang Liu ◽  
Wei Wang ◽  
Yajing Wang ◽  
Zhijun Cao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Response ◽  
Tight Junction ◽  
Lactobacillus Casei ◽  
Mammary Tissue ◽  
Tight Junction Proteins ◽  
E Coli ◽  
Tnf Α ◽  
Injury Models ◽  
Junction Proteins

Escherichia coli is a common mastitis-causing pathogen that can disrupt the blood-milk barrier of mammals. Although Lactobacillus casei Zhang (LCZ) can alleviate mice mastitis, whether it has a prophylactic effect on E. coli-induced mastitis through intramammary infusion, as well as its underlying mechanism, remains unclear. In this study, E. coli-induced injury models of bovine mammary epithelial cells (BMECs) and mice in lactation were used to fill this research gap. In vitro tests of BMECs revealed that LCZ significantly inhibited the E. coli adhesion (p < 0.01); reduced the cell desmosome damage; increased the expression of the tight junction proteins claudin-1, claudin-4, occludin, and zonula occludens-1 (ZO-1; p < 0.01); and decreased the expression of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 (p < 0.01), thereby increasing trans-epithelial electric resistance (p < 0.01) and attenuating the lactate dehydrogenase release induced by E. coli (p < 0.01). In vivo tests indicated that LCZ significantly reduced the injury and histological score of mice mammary tissues in E. coli-induced mastitis (p < 0.01) by significantly promoting the expression of the tight junction proteins claudin-3, occludin, and ZO-1 (p < 0.01), which ameliorated blood-milk barrier disruption, and decreasing the expression of the inflammatory cytokines (TNF-α, IL-1β, and IL-6) in mice mammary tissue (p < 0.01). Our study suggested that LCZ counteracted the disrupted blood-milk barrier and moderated the inflammatory response in E. coli-induced injury models, indicating that LCZ can ameliorate the injury of mammary tissue in mastitis.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252930
Author(s):  
V. Ivashkin ◽  
Y. Poluektov ◽  
E. Kogan ◽  
O. Shifrin ◽  
A. Sheptulin ◽  
...  
Keyword(s):  
Tight Junction ◽  
Healthy Volunteers ◽  
Gut Microbiome ◽  
Low Grade ◽  
Tight Junction Proteins ◽  
Microbiome Composition ◽  
Tnf Α ◽  
Irritable Bowel ◽  
Low Grade Inflammation ◽  
Junction Proteins

Background Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet. Aim of the study To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers. Methods In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-α in mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients. Results The expression of IL-2 and TNF-α was significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05). Conclusion IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Background: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

Sign in / Sign up

Export Citation Format

Share Document