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https://www.readbyqxmd.com/read/29166602/mucus-detachment-by-host-metalloprotease-meprin-%C3%AE-requires-shedding-of-its-inactive-pro-form-which-is-abrogated-by-the-pathogenic-protease-rgpb
#1
Rielana Wichert, Anna Ermund, Stefanie Schmidt, Matthias Schweinlin, Miroslaw Ksiazek, Philipp Arnold, Katharina Knittler, Frederike Wilkens, Barbara Potempa, Björn Rabe, Marit Stirnberg, Ralph Lucius, Jörg W Bartsch, Susanna Nikolaus, Maren Falk-Paulsen, Philip Rosenstiel, Marco Metzger, Stefan Rose-John, Jan Potempa, Gunnar C Hansson, Peter J Dempsey, Christoph Becker-Pauly
The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin β activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin β and is completely inhibited upon its conversion to the active form at the cell surface...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166379/bcfa-enriched-vernix-monoacylglycerol-reduces-lps-induced-inflammatory-markers-in-human-enterocytes-in-vitro
#2
Yuanyuan Yan, Zhen Wang, Donghao Wang, Peter Lawrence, Xingguo Wang, Kumar S D Kothapalli, Jacelyn Greenwald, Ruijie Liu, Hui Gyu Park, J Thomas Brenna
BACKGROUND: Excess vernix caseosa produced by the fetal skin appears as particles suspended in the amniotic fluid in late gestation, is swallowed by the fetus and is found throughout the newborn GI tract as the first organisms are arriving to colonize the gut. Lipid rich vernix contains an unusually high 29% branched chain fatty acid (BCFA). BCFA reduce the incidence of necrotizing enterocolitis in an animal model, recently found predominantly in the sn-2 position of human milk triacylglycerols...
November 22, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29164271/bacteriophages-targeting-intestinal-epithelial-cells-a-potential-novel-form-of-immunotherapy
#3
EDITORIAL
Andrzej Górski, Ewa Jończyk-Matysiak, Marzanna Łusiak-Szelachowska, Ryszard Międzybrodzki, Beata Weber-Dąbrowska, Jan Borysowski
In addition to their established role as a physical barrier to invading pathogens and other harmful agents, intestinal epithelial cells (IEC) are actively involved in local immune reactions. In the past years, evidence has accumulated suggesting the role of IEC in the immunopathology of intestinal inflammatory disorders (IBD). Recent advances in research on bacteriophages strongly suggest that-in addition to their established antibacterial activity-they have immunomodulating properties that are potentially useful in the clinic...
November 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29163538/efficacy-and-safety-of-a-multistrain-probiotic-formulation-depends-from-manufacturing
#4
Vito Trinchieri, Luca Laghi, Beatrice Vitali, Carola Parolin, Ilaria Giusti, Daniela Capobianco, Paola Mastromarino, Claudio De Simone
Background: Variability in probiotics manufacturing may affect their properties, with potential implications for their efficacy and safety. This is of particular concern with probiotic products destined for use in patients with serious medical conditions, including human immunodeficiency virus (HIV) infection. The purpose of the study was to carry out a series of experiments comparing the properties of the US-made probiotic formulation originally commercialized under the brand name VSL#3(®), with those of the Italian-made formulation now commercialized under the same name...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163195/members-of-bitter-taste-receptor-cluster-tas2r143-tas2r135-tas2r126-are-expressed-in-the-epithelium-of-murine-airways-and-other-non-gustatory-tissues
#5
Shuya Liu, Shun Lu, Rui Xu, Ann Atzberger, Stefan Günther, Nina Wettschureck, Stefan Offermanns
The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome) based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29159972/vitamin-b12-deficiency-and-impaired-expression-of-amnionless-during-aging
#6
Alice Pannérec, Eugenia Migliavacca, Antonio De Castro, Joris Michaud, Sonia Karaz, Laurence Goulet, Serge Rezzi, Tze Pin Ng, Nabil Bosco, Anis Larbi, Jerome N Feige
BACKGROUND: Physical frailty and loss of mobility in elderly individuals lead to reduced independence, quality of life, and increased mortality. Vitamin B12 deficiency has been linked to several age-related chronic diseases, including in the musculo-skeletal system, where vitamin B12 deficiency is generally believed to be linked to poor nutritional intake. In the present study, we asked whether aging and frailty associate with altered vitamin B12 homeostasis in humans and investigated the underlying molecular mechanisms using preclinical models...
November 21, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29159350/mucopenetrating-micelles-with-a-peg-corona
#7
Essi M Taipaleenmäki, Sidsel A Mouritzen, Philipp S Schattling, Yan Zhang, Brigitte Städler
Crossing the intestinal mucus layer is a long-standing challenge for orally delivered nanoparticles carrying therapeutic cargo. We report the assembly of mucopenetrating cargo-loaded micelles using block copolymers consisting of either linear poly(ethylene glycol) (PEG) or bottle-brush poly(oligo(ethylene glycol)methacrylate) (PEGb) as the hydrophilic block and poly(caprolactone) (PCL) or poly(cholesteryl methacrylate) (PCMA) as the hydrophobic extension. The micelles were shown to preserve their stability and retain ∼50% of their cargo in simulated gastric fluid...
November 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/29157665/lipopolysaccharide-induced-increase-in-intestinal-epithelial-tight-permeability-is-mediated-by-toll-like-receptor-4-myeloid-differentiation-primary-response-88-myd88-activation-of-myosin-light-chain-kinase-expression
#8
Meghali Nighot, Rana Al-Sadi, Shuhong Guo, Manmeet Rawat, Prashant Nighot, Martin D Watterson, Thomas Y Ma
Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability...
December 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29157080/secretory-autophagy-holds-the-key-to-lysozyme-secretion-during-bacterial-infection-of-the-intestine
#9
Elizabeth Delorme-Axford, Daniel J Klionsky
In 2013, Dr. Lora Hooper and colleagues described the induction of antibacterial macroautophagy/autophagy in intestinal epithelial cells as a cytoprotective host defense mechanism against invading Salmonella enterica serovar Typhimurium (S. Typhimurium). Canonical autophagy functions in a primarily degradative capacity to safeguard cells and ensure survival during stress conditions, including pathogen infection. In contrast, secretory autophagy has emerged as an alternative nondegradative mechanism for cellular trafficking and unconventional protein secretion...
November 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29156831/protective-effect-of-nsa-on-intestinal-epithelial-cells-in-a-necroptosis-model
#10
Wei Dong, Min Zhang, Yaxi Zhu, Yuanhan Chen, Xingchen Zhao, Ruizhao Li, Li Zhang, Zhiming Ye, Xingling Liang
Objective: This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF-α and Z-VAD-fmk, and the cells were treated with or without NSA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156760/microrna-29a-increased-the-intestinal-membrane-permeability-of-colonic-epithelial-cells-in-irritable-bowel-syndrome-rats
#11
Guanqun Chao, Yingying Wang, Shuo Zhang, Weilin Yang, Zheying Ni, Xuliang Zheng
Background: The whole pathogenesis of diarrhea-predominant irritable bowel syndrome(IBS-D) is poorly understood. Our goal was to evaluate the expression change of microRNA-29a(miR-29a) in colonic epithelial cells in IBS rats and clarify the mechanism of miR-29a increasing the intestinal membrane permeability through aquaporins(AQPs). Methods: The IBS-D rats models were induced by rectal distention pressure combining with extremities constraint. The colonic epithelial cells were divided into four groups...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156556/cdx2-stimulates-the-proliferation-of-porcine-intestinal-epithelial-cells-by-activating-the-mtorc1-and-wnt-%C3%AE-catenin-signaling-pathways
#12
Hong-Bo Fan, Zhen-Ya Zhai, Xiang-Guang Li, Chun-Qi Gao, Hui-Chao Yan, Zhe-Sheng Chen, Xiu-Qi Wang
Caudal type homeobox 2 (CDX2) is expressed in intestinal epithelial cells and plays a role in gut development and homeostasis by regulating cell proliferation. However, whether CDX2 cooperates with the mammalian target of rapamycin complex 1 (mTORC1) and Wnt/β-catenin signaling pathways to stimulate cell proliferation remains unknown. The objective of this study was to investigate the effect of CDX2 on the proliferation of porcine jejunum epithelial cells (IPEC-J2) and the correlation between CDX2, the mTORC1 and Wnt/β-catenin signaling pathways...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156489/an-adherent-mucus-layer-attenuates-the-genotoxic-effect-of-colibactin
#13
Christian Reuter, Mona Alzheimer, Heike Walles, Tobias A Oelschlaeger
The human gastrointestinal tract is a complex ecosystem in which epithelial cells and microorganisms of the intestinal microbiota live in symbiosis. Certain members of the microbiota, in particular Escherichia coli strains of the B2 phylotype, carry the polyketide synthase (pks)-island encoding the genotoxin colibactin. Colibactin is a non-ribosomal peptide (NRP) or polyketide (PK)-NRP hybrid of still unsolved structure, which induces DNA double strand breaks (DSBs) in eukaryotic cells. However, direct contact between live bacteria and host cell is required in order to elicit these genotoxic effects...
November 20, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29154988/role-of-p-mkk7-in-myricetin-induced-protection-against-intestinal-ischemia-reperfusion-injury
#14
Yuchao Sun, Mengqiao Lian, Yuan Lin, Bin Xu, Yanli Li, Jin Wen, Dapeng Chen, Ming Xu, Marwan Almoiliqy, Li Wang
Intestinal ischemia reperfusion (I/R) may cause inflammation-, oxidative stress-, and apoptosis-related tissue injuries and facilitate bacterial infection, leading to multiple organ failure. Myricetin, a flavonoid, is found to have diverse biological effects including anti-inflammatory, anti-oxidative, and anti-bacterial effects. Based on our pre-experiment, we proposed that myricetin pretreatment (25, 50mg/kg) could ameliorate intestinal I/R injury and myricetin-induced modulation on MKK7/JNK signal pathway might play a key role in the amelioration...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29153987/development-and-characterization-of-a-human-and-mouse-intestinal-epithelial-cell-monolayer-platform
#15
Kenji Kozuka, Ying He, Samantha Koo-McCoy, Padmapriya Kumaraswamy, Baoming Nie, Karen Shaw, Priscilla Chan, Michael Leadbetter, Limin He, Jason G Lewis, Ziyang Zhong, Dominique Charmot, Marwan Balaa, Andrew J King, Jeremy S Caldwell, Matthew Siegel
We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages...
November 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#16
Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao, Man Chun Chiu, Dong Yang, Yixin Wang, Rex K H Au-Yeung, Ivy Hau-Yee Chan, Shihui Sun, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Ziad A Memish, Victor M Corman, Christian Drosten, Ivan Fan-Ngai Hung, Yusen Zhou, Suet Yi Leung, Kwok-Yung Yuen
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29151691/parallel-mrna-proteomics-and-mirna-expression-analysis-in-cell-line-models-of-the-intestine
#17
Finbarr O'Sullivan, Joanne Keenan, Sinead Aherne, Fiona O'Neill, Colin Clarke, Michael Henry, Paula Meleady, Laura Breen, Niall Barron, Martin Clynes, Karina Horgan, Padraig Doolan, Richard Murphy
AIM: To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. METHODS: Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array...
November 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29148173/metformin-protects-against-intestinal-barrier-dysfunction-via-ampk%C3%AE-1-dependent-inhibition-of-jnk-signalling-activation
#18
Jun Deng, Lishan Zeng, Xueying Lai, Jing Li, Le Liu, Qianyun Lin, Ye Chen
Disruption of the intestinal epithelial barrier, that involves the activation of C-Jun N-terminal kinase (JNK), contributes to initiate and accelerate inflammation in inflammatory bowel disease. Metformin has unexpected beneficial effects other than glucose-lowering effects. Here, we provided evidence that metformin can protect against intestinal barrier dysfunction in colitis. We showed that metformin alleviated dextran sodium sulphate (DSS)-induced decreases in transepithelial electrical resistance, FITC-dextran hyperpermeability, loss of the tight junction (TJ) proteins occludin and ZO-1 and bacterial translocation in Caco-2 cell monolayers or in colitis mice models...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29146676/epithelial-immunity-priming-defensive-responses-in-the-intestinal-mucosa
#19
Cristina Pardo-Camacho, Ana Maria González-Castro, Bruno Kotska Rodiño-Janeiro, Marc Pigrau, Maria Vicario
As the largest interface between the outside and internal milieu, the intestinal epithelium constitutes the first structural component facing potential luminal threats to homeostasis. This single-cell layer is the epicenter of a tightly-regulated communication network between external and internal factors which converge to prime defensive responses aimed at limiting antigen penetration and the maintenance of intestinal barrier function. The defensive role developed by intestinal epithelial cells (IEC) relies largely on the variety of receptors they express at both extracellular (apical and basolateral) and intracellular compartments, and the capacity of IEC to communicate with immune and nervous systems...
November 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29145158/vibrio-cholerae-ompu-induces-il-8-expression-in-human-intestinal-epithelial-cells
#20
Jae Seung Yang, Jun Ho Jeon, Mi Seon Jang, Seok-Seong Kang, Ki Bum Ahn, Manki Song, Cheol-Heui Yun, Seung Hyun Han
Although Vibrio cholerae colonizes the small intestine and induces acute inflammatory responses, less is known about the molecular mechanisms of V. cholerae-induced inflammatory responses in the intestine. We recently reported that OmpU, one of the most abundant outer membrane proteins of V. cholerae, plays an important role in the innate immunity of the whole bacteria. In this study, we evaluated the role of OmpU in induction of IL-8, a representative chemokine that recruits various inflammatory immune cells, in the human intestinal epithelial cell (IEC) line, HT-29...
November 13, 2017: Molecular Immunology
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