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https://www.readbyqxmd.com/read/29033818/itolizumab-a-new-biologic-for-management-of-psoriasis-and-psoriatic-arthritis
#1
Ganesh Pai, Anusha H Pai
Psoriasis is a chronic, relapsing, inflammatory, immune-mediated systemic disease with mainly skin and joint manifestations. The available treatment options to cure psoriasis include topical therapy, phototherapy, and biological therapy. Biological therapy has become a promising option due to the rapid action and less adverse effects associated with its use. The newly developed biologic itolizumab is a humanized recombinant anti-CD6 monoclonal antibody of IgG1 isotype that binds to domain 1 of CD6, thereby immunomodulating human lymphocytes without interfering with the binding of CD6 to the activated leukocyte-cell adhesion molecule...
May 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/29028303/neutrophil-particle-interactions-in-blood-circulation-drive-particle-clearance-and-alter-neutrophil-responses-in-acute-inflammation
#2
Catherine A Fromen, William J Kelley, Margaret B Fish, Reheman Adili, Jeffery Noble, Mark J Hoenerhoff, Michael Holinstat, Omolola Eniola-Adefeso
Although nano- and microparticle therapeutics have been studied for a range of drug delivery applications, the presence of these particles in blood flow may have considerable and understudied consequences to circulating leukocytes, especially neutrophils, which are the largest human leukocyte population. The objective of this work was to establish if particulate drug carriers in circulation interfere with normal neutrophil adhesion and migration. Circulating blood neutrophils in vivo were found to be capable of rapidly binding and sequestering injected carboxylate-modified particles of both 2 µm and 0...
October 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/29023371/expression-profiles-of-ligands-for-activating-natural-killer-cell-receptors-on-hiv-infected-and-uninfected-cd4%C3%A2-%C2%BA-t-cells
#3
Alexandra Tremblay-McLean, Julie Bruneau, Bertrand Lebouché, Irene Lisovsky, Rujun Song, Nicole F Bernard
Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4(-)) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV...
October 12, 2017: Viruses
https://www.readbyqxmd.com/read/29021525/danshenol-a-inhibits-tnf-%C3%AE-induced-expression-of-intercellular-adhesion-molecule-1-icam-1-mediated-by-nox4-in-endothelial-cells
#4
Wenwen Zhao, Haitao Feng, Shuhui Guo, Yantao Han, Xiuping Chen
ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an abietane-type diterpenoid isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular expression are explored. Here, the effect of DA on TNF-α-induced ICAM-1 expression was investigated in endothelial cells. TNF-α-induced ICAM-1 expression and subsequent adhesion of monocytes, as well as elevated reactive oxygen species (ROS) generation and NOX4 expression were all significantly reversed by DA, siNOX4 and NOX4 inhibitor GKT137831...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018081/platelet-interaction-with-activated-endothelium-mechanistic-insights-from-microfluidics
#5
Daniëlle M Coenen, Tom G Mastenbroek, Judith M E M Cosemans
Traditionally, in vitro flow chamber experiments and in vivo arterial thrombosis studies have been proven to be of vital importance to elucidate the mechanisms of platelet thrombus formation after vessel wall injury. In recent years, it has become clear that platelets also act as modulators of inflammatory processes, such as atherosclerosis. A key element herein is the complex crosstalk between platelets, the coagulation system, leukocytes and the activated endothelium. This review provides insight into the platelet-endothelial interface, based on in vitro flow chamber studies and cross referenced with in vivo thrombosis studies...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/29016749/differential-enos-signalling-by-platelet-subpopulations-regulates-adhesion-and-aggregation
#6
Aneta Radziwon-Balicka, Gabriela Lesyk, Valentina Back, Teresa Fong, Erica L Loredo-Calderon, Bin Dong, Haitham El-Sikhry, Ahmed A El-Sherbani, Ayman El-Kadi, Stephen Ogg, Arno Siraki, John M Seubert, Maria Jose Santos-Martinez, Marek W Radomski, Carlos A Velazquez-Martinez, Ian R Winship, Paul Jurasz
Aims: In addition to maintaining hemostasis, circulating blood platelets are the cellular culprits that form occlusive thrombi in arteries and veins. Compared to blood leukocytes, which exist as functionally distinct subtypes, platelets are considered to be relatively simple cell fragments that form vascular system plugs without a differentially regulated cellular response. Hence, investigation into platelet subpopulations with distinct functional roles in hemostasis/thrombosis has been limited...
September 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28994756/screening-assays-to-characterize-novel-endothelial-regulators-involved-in-the-inflammatory-response
#7
María Ángeles Higueras, Lidia Jiménez-García, Sandra Herranz, Sonsoles Hortelano, Alfonso Luque
The endothelial layer is essential for maintaining homeostasis in the body by controlling many different functions. Regulation of the inflammatory response by the endothelial layer is crucial to efficiently fight against harmful inputs and aid in the recovery of damaged areas. When the endothelial cells are exposed to an inflammatory environment, such as the outer component of gram-negative bacteria membrane, lipopolysaccharide (LPS), they express soluble pro-inflammatory cytokines, such as Ccl5, Cxcl1 and Cxcl10, and trigger the activation of circulating leukocytes...
September 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28982599/muscle-derived-extracellular-superoxide-dismutase-inhibits-endothelial-activation-and-protects-against-multiple-organ-dysfunction-syndrome-in-mice
#8
Jarrod A Call, Jean Donet, Kyle S Martin, Ashish K Sharma, Xiaobin Chen, Jiuzhi Zhang, Jie Cai, Carolina A Galarreta, Mitsuharu Okutsu, Zhongmin Du, Vitor A Lira, Mei Zhang, Borna Mehrad, Brian H Annex, Alexander L Klibanov, Russell P Bowler, Victor E Laubach, Shayn M Peirce, Zhen Yan
Multiple organ dysfunction syndrome (MODS) is a detrimental clinical complication in critically ill patients with high mortality. Emerging evidence suggests that oxidative stress and endothelial activation (induced expression of adhesion molecules) of vital organ vasculatures are key, early steps in the pathogenesis. We aimed to ascertain the role and mechanism(s) of enhanced extracellular superoxide dismutase (EcSOD) expression in skeletal muscle in protection against MODS induced by endotoxemia. We showed that EcSOD overexpressed in skeletal muscle-specific transgenic mice (TG) redistributes to other peripheral organs through the circulation and enriches at the endothelium of the vasculatures...
October 2, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28980001/therapeutic-effects-of-ppar%C3%AE-agonist-on-ocular-neovascularization-in-models-recapitulating-neovascular-age-related-macular-degeneration
#9
Fangfang Qiu, Greg Matlock, Qian Chen, Kelu Zhou, Yanhong Du, Xiang Wang, Jian-Xing Ma
Purpose: This study was designed to evaluate effects of fenofibric acid (Feno-FA), a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, on ocular neovascularization (NV) in models recapitulating neovascular age-related macular degeneration (AMD), and to explore whether the effects are PPARα dependent. Methods: Laser-induced choroidal NV (CNV) in rats and very low-density lipoprotein receptor knockout (Vldlr-/-) mice received daily intraperitoneal injections of Feno-FA or vehicle...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28979041/endothelial-glycocalyx-and-cardiopulmonary-bypass
#10
REVIEW
Gerard J Myers, Julie Wegner
On the outer surface of a human cell there is a dense layer of complex carbohydrates called glycocalyx, also referred to as glycans or the sugar coating on the cell surface, which is composed of a complex array of oligosaccharide and polysaccharide glucose chains that are covalently bonded to proteoglycans and lipids bound to the cell membrane surface. Studies of an intact endothelial glycocalyx layer (EGL) have revealed a number of critical functions that relate the importance of this protective layer to vascular integrity and permeability...
September 2017: Journal of Extra-corporeal Technology
https://www.readbyqxmd.com/read/28973837/ezh2-modulates-the-dna-methylome-and-controls-t-cell-adhesion-through-junctional-adhesion-molecule-a-in-lupus-patients
#11
Pei-Suen Tsou, Patrick Coit, Nathan C Kilian, Amr H Sawalha
OBJECTIVE: EZH2 is an epigenetic regulator that mediates H3K27 trimethylation and modulates DNA methylation. The aim of this study is to characterize the role of EZH2 in CD4+ T cells upon lupus pathogenesis. METHODS: EZH2 expression levels were determined in CD4+ T cells isolated from lupus patients and healthy controls. The epigenetic effects of EZH2 overexpression in CD4+ T cells were evaluated using a genome-wide DNA methylation approach. Gene expression and miRNAs were assessed by qPCR while protein expression was examined by Western blotting...
October 3, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28972956/does-polycystic-ovary-syndrome-increase-the-risk-of-subclinical-vascular-disease-in-normal-weight-type-1-diabetic-women
#12
Agnieszka Łebkowska, Agnieszka Adamska, Małgorzata Jacewicz, Joanna Tołwińska, Anna Krentowska, Justyna Hryniewicka, Monika Leśniewska, Artur Bossowski, Maria Górska, Irina Kowalska
INTRODUCTION The prevalence of polycystic ovary syndrome (PCOS) among type 1 diabetic women (T1DM) is higher than in general population. Both diseases are associated with higher risk of premature atherosclerosis. OBJECTIVES The aim of our study was to evaluate whether the cardiovascular risks conferred by T1DM and PCOS are additive. PATIENTS AND METHODS The study group included seventy-eight women divided into 4 groups: 19 women with PCOS and T1DM (T1DM+PCOS), 16 women with T1DM only (T1DM/no-PCOS), 27 women with PCOS only (PCOS), and 16 healthy women (control group)...
September 30, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28972154/neutrophil-microparticle-production-and-inflammasome-activation-by-hyperglycemia-due-to-cytoskeletal-instability
#13
Stephen R Thom, Veena M Bhopale, Kevin Yu, Weiliang Huang, Maureen A Kane, David J Margolis
Microparticles (MPs) are lipid bilayerenclosed vesicles produced by cells under oxidative stress. MPs production is elevated in diabetes but the underlying cellular mechanisms are poorly understood. We hypothesized that raising glucose above the physiological level of 5.5 mM would stimulate leukocytes to produce MPs and activate the nucleotide-binding domain, leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome. We found that when incubated in buffer with up to 20 mM glucose, human and murine neutrophils, but not monocytes, generate progressively more MPs with high interleukin (IL)-1β content...
September 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28971954/dbz-danshensu-bingpian-zhi-a-novel-natural-compound-derivative-attenuates-atherosclerosis-in-apolipoprotein-e-deficient-mice
#14
Jing Wang, Pengfei Xu, Xinni Xie, Jiao Li, Jun Zhang, Jialin Wang, Fan Hong, Jian Li, Youyi Zhang, Yao Song, Xiaohui Zheng, Yonggong Zhai
BACKGROUND: DBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide-induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether DBZ could attenuate atherosclerosis at early and advanced stages. METHODS AND RESULTS: The effects of DBZ on the development of atherosclerosis were studied using apolipoprotein E-deficient (apoE(-/-)) mice...
October 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28968518/beneficial-role-of-the-phytoestrogen-genistein-on-vascular-calcification
#15
Sabrina B Cepeda, Marisa J Sandoval, María B Rauschemberger, Virginia L Massheimer
Although soy phytoestrogen are proposed to prevent or improve postmenopausal vascular and bone diseases, the currently available data are controversial and unclear. In this study we evaluated the molecular and biochemical action of genistein on the cellular events involved in vascular calcification. Rat monocytes, aortic vascular cell and osteoblasts cultures in vitro exposed to Gen were employed. Gen down regulated the expression of cell adhesion molecules involved in stable leukocyte attachment. Using flow cytometry we found that the PE significantly diminished monocyte integrins CD11b, CD11c and CD18 expression either under basal and pro-inflammatory environment...
August 24, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28967906/ezh2-promotes-neoplastic-transformation-through-vav-interaction-dependent-extranuclear-mechanisms
#16
N Venkatesan, J F Wong, K P Tan, H H Chung, Y H Yau, E Cukuroglu, A Allahverdi, L Nordenskiöld, J Göke, S Geifman-Shochat, V C L Lin, M S Madhusudhan, I-H Su
Recently, we reported that the histone methyltransferase, EZH2, controls leukocyte migration through interaction with the cytoskeleton remodeling effector, VAV, and direct methylation of the cytoskeletal regulatory protein, Talin. However, it is unclear whether this extranuclear, epigenetic-independent function of EZH2 has a profound impact on the initiation of cellular transformation and metastasis. Here, we show that EZH2 increases Talin1 methylation and cleavage, thereby enhancing adhesion turnover and promoting accelerated tumorigenesis...
October 2, 2017: Oncogene
https://www.readbyqxmd.com/read/28964848/nerve-glial-antigen-ng-2-is-a-crucial-regulator-of-intercellular-adhesion-molecule-icam-1-expression
#17
Beate M Schmitt, Matthias W Laschke, Oliver G Rössler, Wenhui Huang, Anja Scheller, Michael D Menger, Emmanuel Ampofo
The proteoglycan nerve/glial antigen (NG) 2 is expressed on multiple cell types and mediates cell proliferation and migration. However, little is known about its function in gene regulation. In this study, we demonstrate that in pericytes and glioblastoma cells intercellular adhesion molecule (ICAM)-1, an essential protein for leukocyte adhesion and transmigration, underlies a NG2-dependent expression. As shown by flow cytometry, Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR), silencing of NG2 in human placenta-derived pericytes increased the expression of ICAM-1...
September 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28960175/endothelial-rhob-and-rhoc-are-dispensable-for-leukocyte-diapedesis-and-for-maintaining-vascular-integrity-during-diapedesis
#18
Lilian Schimmel, Aafke de Ligt, Simon Tol, Vivian de Waard, Jaap D van Buul
Active remodeling of the actin cytoskeleton in endothelial cells is necessary for allowing leukocytes to cross the barrier during the process of transendothelial migration (TEM). Involvement of RhoGTPases to regulate actin organization is inevitable, and we recently reported on the local function of RhoA in limiting vascular leakage during leukocyte TEM. As a follow-up we investigated here the possible involvement of two other closely-related GTPases; RhoB and RhoC, in regulating leukocyte TEM and vascular barrier maintenance...
September 29, 2017: Small GTPases
https://www.readbyqxmd.com/read/28943897/role-of-liver-icam-1-in-metastasis
#19
Aitor Benedicto, Irene Romayor, Beatriz Arteta
Intercellular adhesion molecule (ICAM)-1, is a transmembrane glycoprotein of the immunoglobulin (Ig)-like superfamily, consisting of five extracellular Ig-like domains, a transmembrane domain and a short cytoplasmic tail. ICAM-1 is expressed in various cell types, including endothelial cells and leukocytes, and is involved in several physiological processes. Furthermore, it has additionally been reported to be expressed in various cancer cells, including melanoma, colorectal cancer and lymphoma. The majority of studies to date have focused on the expression of the ICAM-1 on the surface of tumor cells, without research into ICAM-1 expression at sites of metastasis...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28939773/pleiotrophin-a-multifunctional-cytokine-and-growth-factor-induces-leukocyte-responses-through-the-integrin-mac-1
#20
Di Shen, Nataly P Podolnikova, Valentin P Yakubenko, Christopher L Ardell, Arnat Balabiyev, Tatiana P Ugarova, Xu Wang
Pleiotrophin (PTN) is a multifunctional, cationic, glycosaminoglycan-binding cytokine and growth factor involved in numerous physiological and pathological processes, including tissue repair and inflammation-related diseases. PTN has been shown to promote leukocyte responses by inducing their migration and expression of inflammatory cytokines. However, the mechanisms through which PTN mediates these responses remain unclear. Here, we identified the integrin Mac-1 (αMβ2, CD11b/CD18) as the receptor mediating macrophage adhesion and migration to PTN...
September 22, 2017: Journal of Biological Chemistry
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