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epithelial barrier

Andrea E Toth, Piotr Siupka, Thomas J P Augustine, Susanne T Venø, Louiza B Thomsen, Torben Moos, Hannes T Lohi, Peder Madsen, Karin Lykke-Hartmann, Morten S Nielsen
Receptor- and adsorptive-mediated transport through brain endothelial cells (BEC) of the blood-brain barrier (BBB) involves a complex array of subcellular vesicular structures, the endo-lysosomal system. It consists of several types of vesicles, such as early, recycling, and late endosomes, retromer-positive structures, and lysosomes. Since this system is important for receptor-mediated transcytosis of drugs across brain capillaries, our aim was to characterise the endo-lysosomal system in BEC with emphasis on their interactions with astrocytes...
March 20, 2018: Molecular Neurobiology
Khaled Elmasry, Riyaz Mohamed, Isha Sharma, Nehal M Elsherbiny, Yutao Liu, Mohamed Al-Shabrawey, Amany Tawfik
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( cbs-/- , cbs+/- and cbs+/+ ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis...
February 27, 2018: Oncotarget
Jason Hellmann, Brian E Sansbury, Blenda Wong, Xiaofeng Li, Mansher Singh, Kristo Nuutila, Nan Chiang, Elof Eriksson, Charles N Serhan, Matthew Spite
Cutaneous injury causes underlying tissue damage that must be quickly repaired to minimize exposure to pathogens and to restore barrier function. While the role of growth factors in tissue repair is established, the role of lipid mediators in skin repair has not been extensively investigated. Using a mass spectrometry-based lipid mediator metabolomics approach, we identified D-series resolvins and related pro-resolving lipid mediators during skin injury in mice and pigs. Differentiation of human epidermal keratinocytes increased expression of 15-lipoxygenase and stereospecific production of 17S-hydroxydocosahexaenoic acid, the common upstream biosynthetic marker and precursor of D-series resolvins...
March 17, 2018: Journal of Investigative Dermatology
Hee Kyoung Chung, Shelley R Wang, Lan Xiao, Navneeta Rathor, Douglas J Turner, Peixin Yang, Myriam Gorospe, Jaladanki N Rao, Jian-Ying Wang
The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and its homeostasis depends on a dynamic balance among proliferation, migration, apoptosis, and differentiation of intestinal epithelial cells (IECs). The PP2A-associated protein α4 controls the activity and specificity of serine/threonine phosphatases and is thus implicated in many cellular processes. Here we investigated the mechanisms whereby α4 controls the homeostasis of the intestinal epithelium using a genetic approach...
March 19, 2018: Molecular and Cellular Biology
Luc Van Kaer, Danyvid Olivares-Villagómez
The intestine is continuously exposed to commensal microorganisms, food, and environmental agents and also serves as a major portal of entry for many pathogens. A critical defense mechanism against microbial invasion in the intestine is the single layer of epithelial cells that separates the gut lumen from the underlying tissues. The barrier function of the intestinal epithelium is supported by cells and soluble factors of the intestinal immune system. Chief among them are intestinal intraepithelial lymphocytes (iIELs), which are embedded in the intestinal epithelium and represent one of the single largest populations of lymphocytes in the body...
April 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Pallavi Gurung, Suhrid Banskota, Nikita Katila, Jaya Gautam, Tara Man Kadayat, Dong-Young Choi, Eung Seok Lee, Tae Cheon Jeong, Jung-Ae Kim
The pathogenesis of inflammatory bowel disease (IBD) is associated with production of immense pro-inflammatory cytokines including TNF-α. Once generated, TNF-α stimulates production of various pro-inflammatory cytokines and disrupts mucosal barrier by inducing inflamed mucosal epithelial cell death. In the present study, we investigated inhibitory effects of TI-1-162, a hydroxyindenone derivative, against TNF-α-induced and TNBS-induced colon inflammation. TI-1-162 showed inhibitory effect on the TNF-α-induced adhesion of U937 monocytic cells to HT-29 colonic epithelial cells (IC50 = 0...
March 16, 2018: European Journal of Pharmacology
Jun Wang, JinXin Lu, XiaoWei Xie, Jia Xiong, Ningning Huang, Hongkui Wei, Siwen Jiang, Jian Peng
Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. The blend of organic acids (OAs) and medium chain fatty acids (MCFAs) has been shown to have synergistic bactericidal effect. In this study, we demonstrated that two blends of OAs and MCFAs (OM1 and OM2) could prevent the inflammatory response and intestinal barrier dysfunction in enterohemorrhagic Escherichia coli (EHEC)-infected mice. Treatments of OM1 and OM2 significantly reduced the body weight loss and production of IL-6 and TNF-α induced by EHEC...
March 16, 2018: International Immunopharmacology
Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A Ashkar, Michel J Tremblay, Dawn Me Bowdish, Charu Kaushic
More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection...
March 19, 2018: Cellular & Molecular Immunology
Tong Shen, Shi Li, Ling-Dong Cai, Jing-Lin Liu, Chu-Yi Wang, Wen-Juan Gan, Xiu-Ming Li, Jing-Ru Wang, Li-Na Sun, Min Deng, Yu-Hong Liu, Jian-Ming Li
The pathogenesis and key functional molecules involved in inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) remain unclear. Here, we reported that Erbin, a protein required for the polarity of epithelial cells, is conserved across species and highly expressed in the intestinal mucosa in mice and zebrafish. Pathologically, Erbin expression in the intestinal mucosa was significantly decreased in DSS induced acute colitis mice, IL-10 deficient mice and clinical biopsy specimens from patients with ulcerative colitis...
February 23, 2018: Oncotarget
Hanwen Tian, Junming Miao, Fumei Zhang, Feng Xiong, Feimei Zhu, Jinyu Li, Xiaoying Wang, Shanzhe Chen, Junli Chen, Ning Huang, Yi Wang
The urinary tract is vulnerable to frequent challenges from environmental microflora. Uropathogenic Escherichia coli (UPEC) makes a major contribution to urinary tract infection (UTI). Previous studies have characterized positive roles of non-histone nuclear protein HMGN2 in lung epithelial innate immune response. In the study presented here, we found HMGN2 expression was up-regulated in UPEC J96-infected urothelium. Surprisingly, over-expression of HMGN2 promoted disruption of BECs 5637 cells' intercellular junctions by down-regulating tight junction (TJs) components' expression and physical structure under J96 infection...
March 17, 2018: Acta Biochimica Polonica
Jonathan J Lyons, Joshua D Milner
Monogenic disorders have provided fundamental insights into human immunity and the pathogenesis of allergic diseases. The pathways identified as critical in the development of atopy range from focal defects in immune cells and epithelial barrier function to global changes in metabolism. A major goal of studying heritable single-gene disorders that lead to severe clinical allergic diseases is to identify fundamental pathways leading to hypersensitivity that can be targeted to provide novel therapeutic strategies for patients with allergic diseases, syndromic and nonsyndromic alike...
March 16, 2018: Journal of Experimental Medicine
D Lapuente, M Storcksdieck Genannt Bonsmann, A Maaske, V Stab, V Heinecke, K Watzstedt, R Heß, A M Westendorf, W Bayer, C Ehrhardt, M Tenbusch
A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies...
March 15, 2018: Mucosal Immunology
Adelaide Tawiah, Steve Cornick, France Moreau, Hayley Gorman, Manish Kumar, Sameer Tiwari, Kris Chadee
MUC2 mucin is a large glycoprotein produced by goblet cells that forms the protective mucus blanket overlying the intestinal epithelium as the first line of innate host defense. High MUC2 production in inflammatory bowel disease and infectious colitis depletes goblet cells and the mucus layer by an unknown mechanism. Here, we analyzed the effect of high MUC2 biosynthesis on endoplasmic reticulum (ER) stress and apoptosis in goblet cells using a high MUC2-producing human goblet cell line (HT29-H) and a HT29-H clone (HT29-L) silenced for MUC2 expression by lentivirus-mediated shRNA...
March 12, 2018: American Journal of Pathology
Jihui Zhang, Jie Chen, Shannon C Mangat, Chathuri Perera Baruhupolage, David R Garrod, Clive Robinson
INTRODUCTION: Intracellular reactive oxidant species (ROS) are generated in human airway epithelial cells by the prothrombinase action of Group 1 house dust mite (HDM) allergens and by ligation of viral RNA sensor Toll-like receptors (TLRs). We explored signaling convergence between HDM allergens and TLRs in ROS generation because epithelial cells form the primary barrier against inhaled substances and dictate host responses to allergens and viruses. METHODS: ROS formation by Calu-3 human airway cells was studied by measuring dihydrorhodamine 123 oxidation after activation by polyinosinic:polycytidylic acid (to activate TLR3), CL097 (to activate TLR7), a natural mixture of HDM allergens, or BzATP...
March 15, 2018: Immunity, Inflammation and Disease
Qiongyuan Hu, Jianan Ren, Guanwei Li, Jie Wu, Xiuwen Wu, Gefei Wang, Guosheng Gu, Huajian Ren, Zhiwu Hong, Jieshou Li
Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls...
March 14, 2018: Cell Death & Disease
Liwei Liu, Jihong Yao, Zhenlu Li, Guo Zu, Dongcheng Feng, Yang Li, Wasim Qasim, Su Zhang, Tong Li, Huizhi Zeng, Xiaofeng Tian
Impairment in gut barrier function induced by intestinal ischemia/reperfusion (I/R) injury is associated with high morbidity and mortality. Intestinal barrier function requires the tight coordination of epithelial migration, proliferation and differentiation. We previously observed that nuclear receptor-related protein 1 (nurr1)-mediated proliferative pathway was impaired in intestinal I/R injury. Here, we aimed to assess the effect of nurr1 on intestinal barrier function and to evaluate microRNA (miRNA)-nurr1-mediated restoration of intestinal barrier function in intestinal I/R injury...
March 14, 2018: Cell Death & Disease
Anita Ferraretto, Michela Bottani, Paola De Luca, Laura Cornaghi, Francesca Arnaboldi, Margherita Maggioni, Amelia Fiorilli, Elena Donetti
An intestinal 70/30 Caco2/HT-29 co-culture was set up starting from the parental populations of differentiated cells to mimic the human intestinal epithelium. Co-culture was harvested at confluence 0 (T0) and at 3, 6, 10 and 14 days of post-confluence after plating (T3, T6, T10 and T14, respectively) for morphological and functional analysis. Transmission electron microscopy revealed different features from T0 to T14: microvilli and a complete junctional apparatus from T6, mucus granules from T3, as also confirmed by PAS/Alcian Blue staining...
March 14, 2018: Bioscience Reports
Xiu-Ting Yu, Yi-Fei Xu, Yan-Feng Huang, Chang Qu, Lie-Qiang Xu, Zi-Ren Su, Hui-Fang Zeng, Lin Zheng, Tie-Gang Yi, Hui-Lin Li, Jian-Ping Chen, Xiao-Jun Zhang
Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism...
2018: PloS One
Mehmet Özbek, Emel Ergün, Feyzullah Beyaz, Levent Ergün, Nuh Y Ld R M, Özge Özgenç, Füsun Erhan
The object of this study was to describe the prenatal development and histochemical properties of mucins in the sheep gastrointestinal tract. To determine changes in the mucin profile, the sections were stained with specific histochemical stains for carbohydrates. While neutral and mixed mucins were observed in the superficial epithelial cells of the abomasal pyloric region, acidic mucins were detected in the secretory ducts and corpus of the glands. Acidic mucins consisted predominantly of sialomucins. In the duodenal villi, the number of goblet cells containing neutral mucins increased toward the end of gestation, whereas Brunner's glands contained acidic mucins until the 95th day of gestation and both acidic and neutral mucins thereafter...
March 14, 2018: Microscopy Research and Technique
Hari R Desu, Laura A Thoma, George C Wood
PURPOSE: Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo...
March 13, 2018: Pharmaceutical Research
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