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https://www.readbyqxmd.com/read/28811631/development-of-a-primary-human-co-culture-model-of-inflamed-airway-mucosa
#1
Lael M Yonker, Hongmei Mou, Kengyeh K Chu, Michael A Pazos, Huimin Leung, Dongyao Cui, Jinhyeob Ryu, Rhianna M Hibbler, Alexander D Eaton, Tim N Ford, J R Falck, T Bernard Kinane, Guillermo J Tearney, Jayaraj Rajagopal, Bryan P Hurley
Neutrophil breach of the mucosal surface is a common pathological consequence of infection. We present an advanced co-culture model to explore neutrophil transepithelial migration utilizing airway mucosal barriers differentiated from primary human airway basal cells and examined by advanced imaging. Human airway basal cells were differentiated and cultured at air-liquid interface (ALI) on the underside of 3 µm pore-sized transwells, compatible with the study of transmigrating neutrophils. Inverted ALIs exhibit beating cilia and mucus production, consistent with conventional ALIs, as visualized by micro-optical coherence tomography (µOCT)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790198/neutrophil-activation-of-endothelial-cell-expressed-trpm2-mediates-transendothelial-neutrophil-migration-and-vascular-injury
#2
Manish Mittal, Saroj Nepal, Yoshikazu Tsukasaki, Claudie M Hecquet, Dheeraj Soni, Jalees Rehman, Chinnaswamy Tiruppathi, Asrar B Malik
Rationale: TRPM2 (Transient Receptor Potential Melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca(2+) entry in response to intracellular generation of adenosine diphosphoribose (ADPR), the TRPM2 ligand. Objective: Because polymorphonuclear leukocytes (PMN) interaction with endothelial cells (ECs) generates ROS, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. Methods and Results: We observed defective PMN transmigration in response to LPS challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2(iΔEC) )...
August 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28770008/overexpression-of-serine-protease-htra-enhances-disruption-of-adherens-junctions-paracellular-transmigration-and-type-iv-secretion-of-caga-by-helicobacter-pylori
#3
Aileen Harrer, Manja Boehm, Steffen Backert, Nicole Tegtmeyer
BACKGROUND: The serine protease HtrA is an important factor for regulating stress responses and protein quality control in bacteria. In recent studies, we have demonstrated that the gastric pathogen Helicobacter pylori can secrete HtrA into the extracellular environment, where it cleaves-off the ectodomain of the tumor suppressor and adherens junction protein E-cadherin on gastric epithelial cells. RESULTS: E-cadherin cleavage opens cell-to-cell junctions, allowing paracellular transmigration of the bacteria across polarized monolayers of MKN-28 and Caco-2 epithelial cells...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28762183/novel-nanoformulation-to-mitigate-co-effects-of-drugs-of-abuse-and-hiv-1-infection-towards-the-treatment-of-neuroaids
#4
Rahul Dev Jayant, Venkata S R Atluri, Sneham Tiwari, Sudheesh Pilakka-Kanthikeel, Ajeet Kaushik, Adriana Yndart, Madhavan Nair
Drug abuse (e.g., methamphetamine-Meth or cocaine-Coc) is one of the major risk factors for becoming infected with HIV-1, and studies show that in combination, drug abuse and HIV-1 lead to significantly greater damage to CNS. To overcome these issues, we have developed a novel nanoformulation (NF) for drug-abusing population infected with HIV-1. In this work, a novel approach was developed for the co-encapsulation of Nelfinavir (Nel) and Rimcazole (Rico) using layer-by-layer (LbL) assembled magnetic nanoformulation for the cure of neuroAIDS...
July 31, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28755848/the-use-of-brazilian-propolis-for-discovery-and-development-of-novel-anti-inflammatory-drugs
#5
REVIEW
Marcelo Franchin, Irlan Almeida Freires, Josy Goldoni Lazarini, Bruno Dias Nani, Marcos Guilherme da Cunha, David Fernando Colón, Severino Matias de Alencar, Pedro Luiz Rosalen
Anti-Inflammatory drugs have been routinely used in the management of acute and chronic inflammatory conditions. Nevertheless, their undesirable side and adverse effects have encouraged the development of more selective, tolerable and efficacious drugs able to modulate the inflammatory process through distinct mechanisms than those of drugs currently available in the market, for instance, inhibition of leukocyte recruitment (chemotaxis, rolling, adhesion and transmigration). Natural products, including Brazilian propolis, have been considered a rich source of anti-inflammatory molecules due to a very complex phytochemical diversity...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28755278/endothelial-bmp4-regulates-leukocyte-diapedesis-and-promotes-inflammation
#6
Thomas Helbing, Linus Arnold, Gwendoline Wiltgen, Eva Hirschbihl, Valentin Gabelmann, Alexandra Hornstein, Jennifer S Esser, Philipp Diehl, Sebastian Grundmann, Hans-Jörg Busch, Katrin Fink, Christoph Bode, Martin Moser
Leukocyte recruitment is a fundamental event in the response of the innate immune system to injury. This process is promoted in part by the opening of endothelial cell adherens junctions that allows leukocyte extravasation through gaps between adjacent endothelial cells. VE-cadherin is a key component of endothelial cell adherens junctions and a negative regulator of leukocyte emigration. Accumulating evidence implicates bone morphogenetic protein (BMP) 4 as a critical regulator in vascular biology, but its role in leukocyte extravasation in vitro and in vivo has not been investigated so far...
July 28, 2017: Inflammation
https://www.readbyqxmd.com/read/28754798/frontline-science-cxcr7-mediates-cd14-cd16-monocyte-transmigration-across-the-blood-brain-barrier-a-potential-therapeutic-target-for-neuroaids
#7
Mike Veenstra, Dionna W Williams, Tina M Calderon, Kathryn Anastos, Susan Morgello, Joan W Berman
CD14(+)CD16(+) monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting >50% of infected individuals...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28740333/mold-alkaloid-cytochalasin-d-modifies-the-morphology-and-secretion-of-fmlp-lps-or-pma-stimulated-neutrophils-upon-adhesion-to-fibronectin
#8
Svetlana I Galkina, Natalia V Fedorova, Marina V Serebryakova, Evgenii A Arifulin, Vladimir I Stadnichuk, Ludmila A Baratova, Galina F Sud'ina
Neutrophils play an essential role in innate immunity due to their ability to migrate into infected tissues and kill microbes with bactericides located in their secretory granules. Neutrophil transmigration and degranulation are tightly regulated by actin cytoskeleton. Invading pathogens produce alkaloids that cause the depolymerization of actin, such as the mold alkaloid cytochalasin D. We studied the effect of cytochalasin D on the morphology and secretion of fMLP-, LPS-, or PMA-stimulated human neutrophils upon adhesion to fibronectin...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28736941/in-vivo-neutralization-of-%C3%AE-4-and-%C3%AE-7-integrins-inhibits-eosinophil-trafficking-and-prevents-lung-injury-during-tropical-pulmonary-eosinophilia-in-mice
#9
Pankaj Sharma, Aditi Sharma, Mrigank Srivastava
Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and β7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and β7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4(+) β7 treatment...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28724302/efficacy-and-safety-of-vedolizumab-as-a-treatment-option-for-moderate-to-severe-refractory-ulcerative-colitis-in-two-patients-after-liver-transplant-due-to-primary-sclerosing-cholangitis
#10
Raúl Vicente Olmedo Martín, Víctor Amo Trillo, Rocío González Grande, Miguel Jiménez Pérez
Vedolizumab is a humanized IgG1 monoclonal antibody that selectively blocks the lymphocyte integrin α4β7 and prevents its interaction with endothelial adhesion molecules and subsequent transmigration to the gastrointestinal tract. The drug was approved in 2014 for the induction and maintenance treatment of ulcerative colitis and moderate to severe Crohn's disease that is refractory or intolerant to conventional treatment with corticoids and immunosuppressants and/or anti-TNFα drugs. However, inflammatory bowel disease has a variable behavior following liver transplant...
July 14, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28710286/how-tetraspanins-shape-endothelial-and-leukocyte-nano-architecture-during-inflammation
#11
REVIEW
Jonas Franz, Marco Tarantola, Christoph Riethmüller
Tetraspanins are ubiquitous membrane proteins that induce local membrane curvature and hence co-ordinate cell-to-cell contacts. This review highlights their role in inflammation, which requires control of the nano-architecture of attachment sites between endothelial cells and leukocytes. The active role of endothelial cells in preparing for transmigration of leukocytes and determining the severity of an inflammation is often underscored. A clear hint to endothelial pre-activation is their ability to protrude clustered adhesion proteins upward prior to leukocyte contact...
August 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28708595/angptl4-promotes-the-progression-of-cutaneous-melanoma-to-brain-metastasis
#12
Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz
In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases.The aim of this study was to determine the functional significance of ANGPTL4 in the shaping of melanoma malignancy phenotype, especially in the establishment of brain metastasis.We confirmed that ANGPTL4 expression is significantly higher in cells metastasizing to the brain than in cells from the cutaneous (local) tumor from the same melanoma in a nude mouse xenograft model, and also in paired clinical specimens of melanoma metastases than in primary melanomas from the same patients...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701303/endothelial-cell-shp-2-negatively-regulates-neutrophil-adhesion-and-promotes-transmigration-by-enhancing-icam-1-ve-cadherin-interaction
#13
Meiping Yan, Xinhua Zhang, Ao Chen, Wei Gu, Jie Liu, Xiaojiao Ren, Jianping Zhang, Xiaoxiong Wu, Aaron T Place, Richard D Minshall, Guoquan Liu
Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration...
July 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28691930/ly6clo-monocytes-drive-immunosuppression-and-confer-resistance-to-anti-vegfr2-cancer-therapy
#14
Keehoon Jung, Takahiro Heishi, Omar F Khan, Piotr S Kowalski, Joao Incio, Nuh N Rahbari, Euiheon Chung, Jeffrey W Clark, Christopher G Willett, Andrew D Luster, Seok Hyun Yun, Robert Langer, Daniel G Anderson, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28688659/indole-3-carbinol-is-a-potent-inhibitor-of-ischemia-reperfusion-induced-inflammation
#15
Emmanuel Ampofo, Nico Lachnitt, Jeannette Rudzitis-Auth, Beate M Schmitt, Michael D Menger, Matthias W Laschke
BACKGROUND: Ischemia-reperfusion (I/R) induces tissue inflammation, which is characterized by an increased leukocyte-endothelial cell interaction and leukocyte transmigration. These processes are mediated by the activation of the nuclear factor (NF)κB signaling pathway, resulting in an elevated expression of specific adhesion molecules. The phytochemical indole-3-carbinol (I3C) has been shown to exert anti-inflammatory effects by interfering with NFκB signal transduction. The aim of the present study was to investigate whether I3C is capable of counteracting the pathogenesis of I/R injury...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28676800/atribacteria-from-the-subseafloor-sedimentary-biosphere-disperse-to-the-hydrosphere-through-submarine-mud-volcanoes
#16
Tatsuhiko Hoshino, Tomohiro Toki, Akira Ijiri, Yuki Morono, Hideaki Machiyama, Juichiro Ashi, Kei Okamura, Fumio Inagaki
Submarine mud volcanoes (SMVs) are formed by muddy sediments and breccias extruded to the seafloor from a source in the deep subseafloor and are characterized by the discharge of methane and other hydrocarbon gasses and deep-sourced fluids into the overlying seawater. Although SMVs act as a natural pipeline connecting the Earth's surface and subsurface biospheres, the dispersal of deep-biosphere microorganisms and their ecological roles remain largely unknown. In this study, we investigated the microbial communities in sediment and overlying seawater at two SMVs located on the Ryukyu Trench off Tanegashima Island, southern Japan...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28663244/frontline-science-c-myc-regulates-p-selectin-glycoprotein-ligand-1-expression-in-monocytes-during-hiv-1-infection
#17
Ryan Connor, Letitia D Jones, Xing Qiu, Juilee Thakar, Sanjay B Maggirwar
Leukocyte extravasation is a crucial feature of the normal immune response to disease and infection and is implicated in various pathologies during chronic inflammatory disease. P-Selectin glycoprotein ligand-1 (PSGL-1) is critical for leukocyte extravasation; however, despite extensive study, it remains unclear how its expression is regulated, which in turn, impedes a more precise understanding of how its expression level affects transmigration. To investigate the regulation of PSGL-1, 60 subjects, with or without HIV infection, were recruited and PSGL-1 expression in monocytes was measured...
June 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28656176/a-three-dimensional-cell-culture-system-to-model-rna-virus-infections-at-the-blood-brain-barrier
#18
John C Bramley, Coyne G Drummond, Nicholas J Lennemann, Charles A Good, Kwang Sik Kim, Carolyn B Coyne
The blood-brain barrier (BBB) comprises the foremost protective barrier in the brain and is composed in part of a layer of microvascular endothelial cells that line the capillaries surrounding the brain. Here, we describe a human three-dimensional (3-D) cell-based model of the BBB microvascular endothelium that recapitulates properties of these cells in vivo, including physiologically relevant transcriptional profiles, the capacity to induce potent antimicrobial innate immune signaling, and the ability to resist infection by diverse RNA viruses, including members of the enterovirus (coxsackievirus B, echovirus 11, enterovirus 71, poliovirus) and flavivirus (dengue virus, Zika virus [ZIKV]) families...
May 2017: MSphere
https://www.readbyqxmd.com/read/28655384/altered-basophil-function-in-patients-with-chronic-kidney-disease-on-hemodialysis%C3%A2
#19
Zenib Aljadi, Anna Nopp, Ola Winqvist, Aman Russom, Britta Hylander, Stefan Jacobson, Joachim Lundahl
AIMS: Chronic kidney disease (CKD) leads to impairment of immune cell function. Given the potential role of basophils in the pathogenesis of CKD, we aimed to study the basophil responsiveness towards microbial antigen exposure, judged as adhesion molecule expression and degranulation, in CKD patients on hemodialysis. MATERIALS AND METHODS: We selected markers linked to two crucial biological phases: the transmigration and degranulation processes, respectively. For the transmigration process, we selected the adhesion molecules CD11b, active CD11b epitope, and CD62L and for the degranulation process CD203c (piecemeal degranulation marker), CD63 (degranulation marker), and CD300a (inhibitory marker of degranulation)...
June 28, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28650050/bilayered-nanofibrous-3d-hierarchy-as-skin-rudiment-by-emulsion-electrospinning-for-burn-wound-management
#20
Pallabi Pal, Prabhash Dadhich, Pavan Kumar Srivas, Bodhisatwa Das, Dhrubajyoti Maulik, Santanu Dhara
Mimicking skin extracellular matrix hierarchy, the present work aims to develop a bilayer skin graft comprising a porous cotton-wool-like 3D layer with membranous structure of PCL-chitosan nanofibers. Emulsion electrospinning with differential stirring periods of PCL-chitosan emulsion results in development of a bilayer 3D structure with varied morphology. The electrospun membrane has fiber diameter ∼274 nm and pore size ∼1.16 μm while fluffy 3D layer has fiber diameter ∼1.62 μm and pore size ∼62 μm...
June 26, 2017: Biomaterials Science
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