scholarly journals Th17 Cytokines Disrupt the Airway Mucosal Barrier in Chronic Rhinosinusitis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Mahnaz Ramezanpour ◽  
Sophia Moraitis ◽  
Jason L. P. Smith ◽  
P. J. Wormald ◽  
Sarah Vreugde
Keyword(s):  
Chronic Rhinosinusitis ◽  
Barrier Function ◽  
Paracellular Permeability ◽  
Mucosal Barrier ◽  
Human Nasal Epithelial Cells ◽  
Basolateral Side ◽  
Junction Protein ◽  
Mucosal Barrier Function ◽  
Th17 Cytokines ◽  
Zona Occludens

Cytokine mediated changes in paracellular permeability contribute to a multitude of pathological conditions including chronic rhinosinusitis (CRS). The purpose of this study was to investigate the effect of interferons and of Th1, Th2, and Th17 cytokines on respiratory epithelium barrier function. Cytokines and interferons were applied to the basolateral side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS with nasal polyp patients. Transepithelial electrical resistance (TEER) and permeability of FITC-conjugated dextrans were measured over time. Additionally, the expression of the tight junction protein Zona Occludens-1 (ZO-1) was examined via immunofluorescence. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Our results showed that application of interferons and of Th1 or Th2 cytokines did not affect the mucosal barrier function. In contrast, the Th17 cytokines IL-17, IL-22, and IL-26 showed a significant disruption of the epithelial barrier, evidenced by a loss of TEER, increased paracellular permeability of FITC-dextrans, and discontinuous ZO-1 immunolocalisation. These results indicate that Th17 cytokines may contribute to the development of CRSwNP by promoting a leaky mucosal barrier.

scholarly journals Dietary fibre affects intestinal mucosal barrier function and regulates intestinal bacteria in weaning piglets

2013 ◽  
Vol 110 (10) ◽  
pp. 1837-1848 ◽  
Author(s):  
Hong Chen ◽  
Xiangbing Mao ◽  
Jun He ◽  
Bing Yu ◽  
Zhiqing Huang ◽  
...  
Keyword(s):  
Barrier Function ◽  
Transforming Growth Factor ◽  
Control Diet ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Mrna Levels ◽  
Intestinal Mucosal Barrier ◽  
Junction Protein ◽  
Mucosal Barrier Function ◽  
Weaning Piglets

The objective of the present study was to evaluate the effects of fibre source on intestinal mucosal barrier function in weaning piglets. A total of 125 piglets were randomly allotted on the basis of their body weight and litters to one of five experimental diets, i.e. a control diet without fibre source (CT), and diets in which expanded maize was replaced by 10 % maize fibre (MF), 10 % soyabean fibre (SF), 10 % wheat bran fibre (WBF) or 10 % pea fibre (PF). The diets and water were fed ad libitum for 30 d. Piglets on the WBF and PF diets had lower diarrhoea incidence compared with the MF- and SF-fed animals. A higher ratio of villous height:crypt depth in the ileum of WBF-fed piglets and higher colonic goblet cells in WBF- and PF-fed piglets were observed compared with CT-, MF- and SF-fed piglets. In the intestinal digesta, feeding WBF and PF resulted in increased Lactobacillus counts in the ileum and Bifidobacterium counts in the colon. Lower Escherichia coli counts occurred in the ileum and colon of WBF-fed piglets than in SF-fed piglets. Tight junction protein (zonula occludens 1; ZO-1) and Toll-like receptor 2 (TLR2) gene mRNA levels were up-regulated in the ileum and colon of pigs fed WBF; however, feeding MF and SF raised IL-1α and TNF-α mRNA levels. Furthermore, higher diamine oxidase activities, transforming growth factor-α, trefoil factor family and MHC-II concentration occurred when feeding WBF and PF. In conclusion, the various fibre sources had different effects on the ileal and colonic barrier function. Clearly, WBF and PF improved the intestinal barrier function, probably mediated by changes in microbiota composition and concomitant changes in TLR2 gene expression.

scholarly journals Konjac glucomannan polysaccharide and inulin oligosaccharide enhance the colonic mucosal barrier function and modulate gut-associated lymphoid tissue immunity in C57BL/6J mice

2019 ◽  
Vol 123 (3) ◽  
pp. 319-327 ◽  
Author(s):  
Chih-Hsuan Changchien ◽  
Yi-Chun Han ◽  
Hsiao-Ling Chen
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Barrier Function ◽  
Control Diet ◽  
Konjac Glucomannan ◽  
Mucosal Barrier ◽  
Low Level ◽  
Inflammatory Status ◽  
Junction Protein ◽  
Mucosal Barrier Function

AbstractBoth konjac glucomannan (KGM) and inulin oligosaccharide have been shown to improve bowel function, but their effects on the mucosal barrier function and immunity are not fully understood. The aim of the present study was to determine the effects of a low-level supplementation of dietary fibres on the colonic mucosal barrier function, antioxidant enzyme defence and immunity. C57BL/6J mice (6 weeks of age, eight per group) were randomly assigned to consume one of the following diets: control or control diet supplemented with 2 % (w/w) of KGM, inulin oligosaccharide (degree polymerisation = 8) or KGM+inulin (1 %, w/w each (K+I)). Fresh faeces were collected on days 19–21. Mice were killed on day 22 after fasting. Segments of colon tissues were processed for histological procedure and stained for acidic mucins and tight junction protein marker zona occludin-1 (ZO-1). The remaining tissues were processed to determine the gene expression of mucin 2, tight junction proteins, antioxidant enzymes and cytokines. The plasma cytokines were measured. Results indicated that KGM, inulin and K+I significantly increased the mucosal layer thickness, mucin density (granule number/crypt) and gene expression of Muc2 as compared with the control. All fibre treatments increased the gene expressions of ZO-1, occludin, glutathione peroxidase, glutathione S-transferase π, catalase and IL-10. In addition, all fibre treatments increased faecal butyrate and probiotics, and plasma IL-10 concentrations. In conclusion, supplementation of low-level, 2 % (w/w), of K+I was sufficient to enhance the mucosal barrier function and anti-inflammatory status.

Chloride channel ClC-2 modulates tight junction barrier function via intracellular trafficking of occludin

2012 ◽  
Vol 302 (1) ◽  
pp. C178-C187 ◽  
Author(s):  
Prashant K. Nighot ◽  
Anthony T. Blikslager
Keyword(s):  
Mass Spectrometry ◽  
Tight Junction ◽  
Chloride Channel ◽  
Barrier Function ◽  
Intracellular Trafficking ◽  
Cell Clone ◽  
Mucosal Barrier ◽  
Caveolin 1 ◽  
Junction Protein ◽  
Mucosal Barrier Function

Previously, we have demonstrated that the chloride channel ClC-2 modulates intestinal mucosal barrier function. In the present study, we investigated the role of ClC-2 in epithelial barrier development and maintenance in Caco-2 cells. During early monolayer formation, silencing of ClC-2 with small interfering (si)RNA led to a significant delay in the development of transepithelial resistance (TER) and disruption of occludin localization. Proteomic analysis employing liquid chromatography-mass spectrometry /mass spectrometry revealed association of ClC-2 with key proteins involved in intracellular trafficking, including caveolin-1 and Rab5. In ClC-2 siRNA-treated cells, occludin colocalization with caveolin-1 was diffuse and in the subapical region. Subapically distributed occludin in ClC-2 siRNA-treated cells showed marked colocalization with Rab5. To study the link between ClC-2 and trafficking of occludin in confluent epithelial monolayers, a Caco-2 cell clone expressing ClC-2 short hairpin (sh)RNA was established. Disruption of caveolae with methyl-β-cyclodextrin (MβCD) caused a marked drop in TER and profound redistribution of caveolin-1-occludin coimmunofluorescence in ClC-2 shRNA cells. In ClC-2 shRNA cells, focal aggregations of Rab5-occludin coimmunofluorescence were present within the cytoplasm. Wortmannin caused an acute fall in TER in ClC-2 shRNA cells and subapical, diffuse redistribution of Rab5-occludin coimmunofluorescence in ClC-2 shRNA cells. An endocytosis and recycling assay for occludin revealed higher basal rate of endocytosis of occludin in ClC-2 shRNA cells. Wortmannin significantly reduced the rate of recycling of occludin in ClC-2 shRNA cells. These data clearly indicate that ClC-2 plays an important role in the modulation of tight junctions by influencing caveolar trafficking of the tight junction protein occludin.

Physiological concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum

2004 ◽  
Vol 287 (2) ◽  
pp. G399-G407 ◽  
Author(s):  
Nigel B. Campbell ◽  
Craig G. Ruaux ◽  
Donnie E. Shifflett ◽  
Jöerg M. Steiner ◽  
David A. Williams ◽  
...  
Keyword(s):  
Barrier Function ◽  
Bile Salts ◽  
Deoxycholic Acid ◽  
Paracellular Permeability ◽  
Mucosal Barrier ◽  
Histological Evaluation ◽  
Ileal Mucosa ◽  
Ussing Chambers ◽  
Mucosal Barrier Function ◽  
Mannitol Flux

We have previously shown rapid in vitro recovery of barrier function in porcine ischemic-injured ileal mucosa, attributable principally to reductions in paracellular permeability. However, these experiments did not take into account the effects of luminal contents, such as bile salts. Therefore, the objective of this study was to evaluate the role of physiological concentrations of deoxycholic acid in recovery of mucosal barrier function. Porcine ileum was subjected to 45 min of ischemia, after which mucosa was mounted in Ussing chambers and exposed to varying concentrations of deoxycholic acid. The ischemic episode resulted in significant reductions in transepithelial electrical resistance (TER), which recovered to control levels of TER within 120 min, associated with significant reductions in mucosal-to-serosal 3H-labeled mannitol flux. However, treatment of ischemic-injured tissues with 10−5 M deoxycholic acid significantly inhibited recovery of TER with significant increases in mucosal-to-serosal 3H-labeled mannitol flux, whereas 10−6 M deoxycholic acid had no effect. Histological evaluation at 120 min revealed complete restitution regardless of treatment, indicating that the breakdown in barrier function was due to changes in paracellular permeability. Similar effects were noted with the application of 10−5 M taurodeoxycholic acid, and the effects of deoxycholic acid were reversed with application of the Ca2+-mobilizing agent thapsigargin. Deoxycholic acid at physiological concentrations significantly impairs recovery of epithelial barrier function by an effect on paracellular pathways, and these effects appear to be Ca2+ dependent.

Glucagon-Like Peptide-2 Improve Intestinal Mucosal Barrier Function in Aged Rats

2018 ◽  
Vol 22 (6) ◽  
pp. 731-738 ◽  
Author(s):  
Weiying Ren ◽  
Jiayu Wu ◽  
Li Li ◽  
Y. Lu ◽  
Y. Shao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Mucosal Barrier ◽  
Aged Rats ◽  
Intestinal Mucosal Barrier ◽  
Mucosal Barrier Function ◽  
Glucagon Like Peptide
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