Tight junction molecules are unresponsive in the epithelium of COPD patients during RV infection

Author(s):  
Rassin Lababidi ◽  
Jennifer Cane ◽  
Mona Bafadhel
2019 ◽  
Vol 68 (1) ◽  
pp. 59-72 ◽  
Author(s):  
Takumi Konno ◽  
Takayuki Kohno ◽  
Shin Kikuchi ◽  
Hiroshi Shimada ◽  
Seiro Satohisa ◽  
...  

Epithelial integrity and barrier function are maintained during cytokinesis in vertebrate epithelial tissues. The changes in localization and the roles of tricellular tight junction molecule lipolysis-stimulated lipoprotein receptor (LSR) during cytokinesis are not well known, although new tricellular tight junctions form at the flank of the midbody during cytokinesis. In this study, we investigated the changes in localization and the role of LSR at the midbody and centrosome during cytokinesis using human endometrial carcinoma cell line Sawano, comparing the tricellular tight junction molecule tricellulin; bicellular tight junction molecules occludin, claudin-7, zonula occludens-1, and cingulin; and the epithelial polarized related molecules apoptosis-stimulating of p53 protein 2, PAR3, and yes-associated protein. During cytokinesis induced by treatment with taxol, the epithelial barrier was maintained and the tricellular tight junction molecules LSR and tricellulin were concentrated at the flank of the acetylated tubulin–positive midbody and in γ-tubulin-positive centrosomes with the dynein adaptor Hook2, whereas the other molecules were localized there as well. All the molecules disappeared by knockdown using small interfering RNAs. Furthermore, by the knockdown of Hook2, the epithelial barrier was maintained and most of the molecules disappeared from the centrosome. These findings suggest that LSR may play crucial roles not only in barrier function but also in cytokinesis.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Takashi Kojima ◽  
Mitsuru Go ◽  
Ken-ichi Takano ◽  
Makoto Kurose ◽  
Tsuyoshi Ohkuni ◽  
...  

The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs) are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP), which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECsin vitroinduces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261189
Author(s):  
Wimonrat Panpetch ◽  
Peerapat Visitchanakun ◽  
Wilasinee Saisorn ◽  
Ajcharaporn Sawatpanich ◽  
Piraya Chatthanathon ◽  
...  

Because of a possible impact of capsaicin in the high concentrations on enterocyte injury (cytotoxicity) and bactericidal activity on probiotics, Lactobacillus rhamnosus L34 (L34) and Lactobacillus rhamnosus GG (LGG), the probiotics derived from Thai and Caucasian population, respectively, were tested in the chili-extract administered C57BL/6 mice and in vitro experiments. In comparison with placebo, 2 weeks administration of the extract from Thai chili in mice caused loose feces and induced intestinal permeability defect as indicated by FITC-dextran assay and the reduction in tight junction molecules (occludin and zona occludens-1) using fluorescent staining and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the chili extracts also induced the translocation of gut pathogen molecules; lipopolysaccharide (LPS) and (1→3)-β-d-glucan (BG) and fecal dysbiosis (microbiome analysis), including reduced Firmicutes, increased Bacteroides, and enhanced total Gram-negative bacteria in feces. Both L34 and LGG attenuated gut barrier defect (FITC-dextran, the fluorescent staining and gene expression of tight junction molecules) but not improved fecal consistency. Additionally, high concentrations of capsaicin (0.02–2 mM) damage enterocytes (Caco-2 and HT-29) as indicated by cell viability test, supernatant cytokine (IL-8), transepithelial electrical resistance (TEER) and transepithelial FITC-dextran (4.4 kDa) but were attenuated by Lactobacillus condition media (LCM) from both probiotic-strains. The 24 h incubation with 2 mM capsaicin (but not the lower concentrations) reduced the abundance of LGG (but not L34) implying a higher capsaicin tolerance of L34. However, Lactobacillus rhamnosus fecal abundance, using qRT-PCR, of L34 or LGG after 3, 7, and 20 days of the administration in the Thai healthy volunteers demonstrated the similarity between both strains. In conclusion, high dose chili extracts impaired gut permeability and induced gut dysbiosis but were attenuated by probiotics. Despite a better capsaicin tolerance of L34 compared with LGG in vitro, L34 abundance in feces was not different to LGG in the healthy volunteers. More studies on probiotics with a higher intake of chili in human are interesting.


2011 ◽  
Vol 18 (3) ◽  
pp. 593-606 ◽  
Author(s):  
Anna-Mária Tőkés ◽  
Attila Marcell Szász ◽  
Éva Juhász ◽  
Zsuzsa Schaff ◽  
László Harsányi ◽  
...  

2020 ◽  
Author(s):  
Yizi Cong ◽  
Yuxin Cui ◽  
Shiguang Zhu ◽  
Jianqiao Cao ◽  
Guangdong Qiao ◽  
...  

Abstract Background: T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, but its exact role in breast cancer has not been fully elucidated. Methods: The gene expression level of Tim-3 in breast cancer and its prognostic significance were analysed. In vitro functions and associated mechanisms were then explored through establishing Tim-3 overexpressing breast cancer cells. Results: The gene expression level of Tim-3 was significantly higher (p<0.001) in breast cancer tissue compared to normal tissue following pooled analysis of the TCGA database. Tim-3 was a prognosis indicator in breast cancer patients as shown by KM-plotter (RFS: p=0.004; OS: p=0.099). Overexpression of the Tim-3 in Tim-3 low breast cancer cells promoted aggressiveness of breast cancer cells including proliferation, migration, invasion, tight junction deterioration and tumour-associated tubal formation. Furthermore, Tim-3 enhanced cellular resistance to paclitaxel. Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway, and mediating gene regulation (upregulating CCND1, C-Myc, MMP1, TWIST, VEGF while downregulating E-cadherin). Additionally, Tim-3 downregulated tight junction molecules: ZO-2, ZO-1 and Occludin, which might further facilitate the tumour progression. Conclusions: Tim-3 plays a tumour-promoting role in breast cancer, suggesting that targeting Tim-3 may acquire a clinical benefit in antitumor therapy. Keywords: breast cancer, Tim-3, tight junction, chemoresistance, aggressiveness.


2005 ◽  
Vol 58 (4) ◽  
pp. 791-798 ◽  
Author(s):  
Praveen Ballabh ◽  
Furong Hu ◽  
Mithun Kumarasiri ◽  
Alex Braun ◽  
Maiken Nedergaard

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