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Tight junctions claudin

Julia Gauberg, Dennis Kolosov, Scott P Kelly
This study examined regional distribution and corticosteroid-induced alterations of claudin (cldn) transcript abundance in teleost fish skin. Regional comparison of mRNA encoding 20 Cldns indicated that 12 exhibit differences in abundance along the dorsoventral axis of skin. However, relative abundance of cldns (i.e. most to least abundant) remained similar in different skin regions. Several cldns appear to be present in the epidermis and dermal vasculature whereas others are present only in the epidermis. Increased circulating cortisol levels significantly altered mRNA abundance of 10 cldns in a region specific manner, as well as corticosteroid receptors and 11β-hydroxysteroid dehydrogenase (type 2)...
October 19, 2016: General and Comparative Endocrinology
Yuka Nakaya, Mayu Takaya, Yuta Hinatsu, Tammam Alama, Kosuke Kusamori, Hidemasa Katsumi, Toshiyasu Sakane, Akira Yamamoto
Bisphosphonates (BPs) are carbon-substituted pyrophosphate analogs that exhibit a high affinity to hydroxyapatite and specifically inhibit bone resorption. Alendronate sodium (sodium 4-amino-1-hydroxybutylidene-1,1-bisphosphonate trihydrate) is a typical BP compound in clinical use. BPs have very low bioavailability, typically <1% after their oral administration, and their intestinal absorption is further reduced by co-administered drugs or food. In this study, we examined the effects of N-acyl amino acids and N-acyl taurates on the small intestinal absorption of alendronate...
October 19, 2016: Journal of Pharmaceutical Sciences
Joshua B Lewis, Dallin C Milner, Adam L Lewis, Todd M Dunaway, Kaleb M Egbert, Scott C Albright, Brigham J Merrell, Troy D Monson, Dallin S Broberg, Jason R Gassman, Daniel B Thomas, Juan A Arroyo, Paul R Reynolds
It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung...
October 17, 2016: International Journal of Environmental Research and Public Health
Yuan Zhou, Xiaoping Xu, Beibei Yu, Guang Yu
The intestinal epithelium is a single-cell layer that provides an important barrier against natural toxins. Microcystin-LR (MC-LR), a cyclic heptapeptide, is one of the best known toxins able to alter the functions of intestine. This study evaluated the toxic effects and the possible mechanisms of MC-LR on barrier function of the intestinal epithelial cells. Intestinal epithelial cells (IEC-6) were exposed to 0, 6.25, 12.5, 25 and 50 μM MC-LR. Cell viability significantly decreased, while the ratio of apoptotic cells increased after exposure to 12...
October 19, 2016: Environmental Toxicology
Gheun-Ho Kim, Chor Ho Jo, Sua Kim, Il Hwan Oh, Joon-Sung Park
OBJECTIVE: Claudins are tight junction proteins that regulate paracellular permeability of renal epithelia, and renal paracellular sodium chloride permeability may be essential to salt homeostasis and blood pressure control. A previous study has shown that the collecting duct-specific claudin-4 knockout animals develop hypotension due to profound renal wasting of chloride. This study was undertaken to investigate whether claudins have a role in the hypertension of Dahl salt-sensitive (DS) rats...
September 2016: Journal of Hypertension
Raphaela Mayerhofer, Esther E Fröhlich, Florian Reichmann, Aitak Farzi, Nora Kogelnik, Eleonore Fröhlich, Wolfgang Sattler, Peter Holzer
Microbial metabolites are known to affect immune system, brain, and behavior via activation of pattern recognition receptors such as Toll-like receptor 4 (TLR4). Unlike the effect of the TLR4 agonist lipopolysaccharide (LPS), the role of other TLR agonists in immune-brain communication is insufficiently understood. We therefore hypothesized that the TLR2 agonist lipoteichoic acid (LTA) causes immune activation in the periphery and brain, stimulates the hypothalamic-pituitary-adrenal (HPA) axis and has an adverse effect on blood-brain barrier (BBB) and emotional behavior...
October 14, 2016: Brain, Behavior, and Immunity
Y-B Yu, D-Y Zhao, Q-Q Qi, X Long, X Li, F-X Chen, X-L Zuo
BACKGROUND: Brain-derived neurotrophic factor (BDNF) may play a vital role in the homeostatic regulation of intestinal barrier integrity. We aimed to investigate the physiological role of BDNF in maintaining the intestinal epithelial barrier using postinflammatory irritable bowel syndrome (PI-IBS) mice and explore the underlying molecular mechanisms using intestinal epithelial cells in vitro. METHODS: Postinflammatory-IBS mice were induced by intrarectal administration of trinitrobenzene sulfonic acid and allowed to recover for 28 days...
October 17, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
I C Sampaio, P H Q S Medeiros, F A P Rodrigues, P A Cavalcante, S A Ribeiro, J S Oliveira, M M G Prata, D V S Costa, S G C Fonseca, M M Guedes, A M Soares, G A C Brito, A Havt, S R Moore, A A M Lima
Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions...
October 10, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Naoko Fujii, Yukinobu Matsuo, Toshiyuki Matsunaga, Satoshi Endo, Hideki Sakai, Masahiko Yamaguchi, Yasuhiro Yamazaki, Junko Sugatani, Akira Ikari
Hypotonic stress decreased claudin-1 and -2 expression levels in renal tubular epithelial HK-2 and Madin-Darby canine kidney cells. Here, we examined the regulatory mechanism involved in this decrease. The hypotonic-induced decrease in claudin expression was inhibited by SB202190, a p38 mitogen-activated protein kinase inhibitor, but not by U0126, a MEK inhibitor, Go6983, a protein kinase C inhibitor, or SP600125, a Jun N-terminal protein kinase inhibitor. Hypotonic stress increased transepithelial electrical resistance, which was inhibited by SB202190...
October 12, 2016: Journal of Biological Chemistry
Kevin Looi, Niamh M Troy, Luke W Garratt, Thomas Iosifidis, Anthony Bosco, Alysia G Buckley, Kak-Ming Ling, Kelly M Martinovich, Elizabeth Kicic-Starcevich, Nicole C Shaw, Erika N Sutanto, Graeme R Zosky, Paul J Rigby, Alexander N Larcombe, Darryl A Knight, Anthony Kicic, Stephen M Stick
RATIONALE: No studies have assessed the effects of human rhinovirus (HRV) infection on epithelial tight junctions (TJs) and resultant barrier function. AIM OF THE STUDY: To correlate viral infection with TJ disassembly, epithelial barrier integrity, and function. MATERIALS AND METHODS: Human airway epithelial cells were infected with HRV minor serotype 1B (HRV-1B) at various 50% tissue culture infectivity doses (TCID50) over 72 hours. HRV replication was assessed by quantitative-polymerase chain reaction (qPCR) while cell viability and apoptosis were assessed by proliferation and apoptotic assays, respectively...
October 11, 2016: Experimental Lung Research
Frances Corrigan, Kimberley A Mander, Anna V Leonard, Robert Vink
BACKGROUND: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. MAIN BODY: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI...
October 11, 2016: Journal of Neuroinflammation
Yosuke Hashimoto, Yumi Kawahigashi, Tomoyuki Hata, Xiangru Li, Akihiro Watari, Minoru Tada, Akiko Ishii-Watabe, Yoshiaki Okada, Takefumi Doi, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
Claudin-4 (CLDN-4), a tight-junction protein, is overexpressed in various malignant tumors, including gastric, colorectal, pancreatic, and breast cancers. However, CLDN-4 is also expressed in normal tissues, including the liver, pancreas, kidney, and small intestine. Whether CLDN-4 is an effective and safe target for cancer therapy has been unclear owing to the lack of a binder with both CLDN-4 specificity and cross-reactivity to human and murine cells. In this study, we successfully generated a rat anti-CLDN-4 monoclonal antibody (5D12) that was specific to, and cross-reactive with, human and mouse CLDN-4...
October 2016: Pharmacology Research & Perspectives
Junwei Xu, Lu Lu, Jing Lu, Jihui Xia, Hongjin Lu, Lin Yang, Wensheng Xia, Shihai Shen
BACKGROUND: Recent evidence suggests that CD200 fusion protein (CD200Fc), a CD200R1 agonist may attenuate inflammatory responses in autoimmune diseases and neuro-degeneration. While, little is known about the function of CD200Fc in cigarette smoke extract (CSE)-induced mouse Cardiac Microvascular Endothelial Cells (mCMECs). The present study was designed to elucidate the effects of CD200Fc on CSE-induced vascular endothelial barrier (VEB) dysfunction and inflammatory responses, which is a highly clinically relevant model of smoking related cardiovascular diseases...
October 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Fernando Garcia-Polite, Jordi Martorell, Paula Del Rey-Puech, Pedro Melgar-Lesmes, Caroline C O'Brien, Jaume Roquer, Angel Ois, Alessandro Principe, Elazer R Edelman, Mercedes Balcells
Microvascular endothelial cells at the blood-brain barrier exhibit a protective phenotype, which is highly induced by biochemical and biomechanical stimuli. Amongst them, shear stress enhances junctional tightness and limits transport at capillary-like levels. Abnormal flow patterns can reduce functional features of macrovascular endothelium. We now examine if this is true in brain microvascular endothelial cells. We suggest in this paper a complex response of endothelial cells to aberrant forces under different flow domains...
October 4, 2016: Journal of Cerebral Blood Flow and Metabolism
Bingjie Wang, Brian J McHugh, Ayub Qureshi, Dominic J Campopiano, David J Clarke, J Ross Fitzgerald, Julia R Dorin, Richard Weller, Donald J Davidson
Atopic Dermatitis (AD) is a common chronic inflammatory skin disease, resulting in significant morbidity. A hallmark of AD is disruption of the critical barrier function of upper epidermal layers, causatively linked to environmental stimuli, genetics and infection, and a critical current target for the development of new therapeutic and prophylactic interventions. S. aureus is an AD-associated pathogen producing virulence factors which induce skin barrier disruption in vivo and contribute to AD pathogenesis...
September 9, 2016: Journal of Investigative Dermatology
Pei Wu, Wei-Dan Jiang, Jun Jiang, Juan Zhao, Yang Liu, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study investigated the effects of choline on intestinal mucosal immune and the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65 days. The results firstly showed that choline deficiency induced inflammatory infiltration in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of fish. Meanwhile, compared with the optimal choline group, choline deficiency decreased the activities of lysozyme and acid phosphatase, contents of complement 3 and IgM in the intestine, downregulated the mRNA levels of antimicrobial peptides (liver-expressed antimicrobial peptide (LEAP) 2A and defensin-3 in the PI and MI, LEAP-2B and hepcidin in the PI, MI and DI), anti-inflammatory cytokines (interleukin (IL) 10 and transforming growth factor β2 in the PI, MI and DI), and signaling molecule IκB in the PI, MI and DI; while upregulated the mRNA levels of pro-inflammatory cytokines (IL-6a and tumor necrosis factor α in the MI and DI, interferon γ2b in the PI and MI, IL-1β and IL-6b in the PI, MI and DI), and signaling molecules (Toll-like receptor 4 in the MI, myeloid differentiation primary response 88 in the PI and MI, Janus kinase 3 and tyrosine kinase 2 in the MI and DI, nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STAT) 4 and STAT5 in the PI, MI and DI) of juvenile Jian carp, further indicating that choline deficiency caused inflammation and immunity depression in the intestine of fish...
September 28, 2016: Fish & Shellfish Immunology
I-Chieh Chen, I-Lun Hsiao, Ho-Chen Lin, Chien-Hou Wu, Chun-Yu Chuang, Yuh-Jeen Huang
An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8nm) and TiO2 nanoparticles (TiO2NPs; 6nm and 35nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB...
September 15, 2016: Environmental Toxicology and Pharmacology
Maryline C Bossus, Rebecca J Bollinger, P Justin Reed, Christian K Tipsmark
Several gill claudin (Cldn) tight junction proteins in Japanese medaka are regulated by salinity (cldn10 paralogs and cldn28b), while others are constitutively expressed (cldn27a, cldn28a and cldn30c). The role of the endocrine system in this regulation has yet to be understood. The in vitro effects of cortisol and prolactin on cldn expression in gill explant cultures were investigated in medaka. ncc2b and cftr were used as markers of specific ionocytes associated with freshwater- and seawater-acclimation, respectively...
September 20, 2016: General and Comparative Endocrinology
Xue-Feng Shen, Ping Huang, Donald A Fox, Yan Lin, Zai-Hua Zhao, Wen Wang, Ji-Ye Wang, Xin-Qin Liu, Jing-Yuan Chen, Wen-Jing Luo
Low-to-moderate level developmental and adult lead exposure produces retinal dysfunction and/or degeneration in humans and experimental animals. Although high level in vivo or in vitro lead disrupts blood-brain-barrier tight junctions and increases its permeability, the blood-retinal-barrier (BRB) has not been examined. There were four overall goals. First, generate environmentally relevant dose-response models of short-term lead exposure in adult rats. Second, assess retinal histology and functional integrity of the BRB...
September 20, 2016: Neurotoxicology
K Barth, R Bläsche, A Neißer, S Bramke, J A Frank, M Kasper
The purinergic receptor P2X7 represents an ATP-gated ionotropic receptor with a selective localization in alveolar epithelial type I cells of the lung. Despite the involvement of the receptor in inflammatory processes of the lung, it is not established whether this receptor plays a specific role in the alveolar epithelial cell biology. There is evidence that P2X7 receptor influences Wnt/β-catenin signalling pathways in alveolar epithelial cells under conditions of injury. Here, we investigated the expression of GSK-3β, a potent protein kinase involved in alveolar epithelial barrier functions, and of tight junction molecules occludin, claudin-4 and claudin-18 in wild-type and P2X7(-/-) mice...
September 23, 2016: Histochemistry and Cell Biology
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