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Mario T Schellenberger, Udo Bock, Jennifer Hennen, Florian Groeber-Becker, Heike Walles, Brunhilde Blömeke
A key event of the adverse outcome pathway for skin sensitization is the activation of dendritic cells (DC). To be most close to the in vivo situation, we combined for the first time reconstructed human epidermis (RHE) in coculture with THP-1 cells, as surrogate for DC. THP-1 cells were placed underneath RHE (SkinEthic™, OS-REp). Cell activation was measured by analyzing cell surface expression of co-stimulatory molecules CD86 and CD40, adhesion molecule CD54 and of human leukocyte antigen class II-related subtypes (HLA-DR) on THP-1 cells by flow cytometry...
February 13, 2019: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Laura Atehortúa, Mauricio Rojas, Gloria Vásquez, Carlos H Muñoz-Vahos, Adriana Vanegas-García, Rafael Andrés Posada-Duque, Diana Castaño
BACKGROUND: Endothelial activation and damage is commonly observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is related to development of atherosclerosis and cardiovascular diseases. Different components of the immune system seem to participate in the endothelial injury, such as generation of autoantibodies and formation of immune complexes (ICs). Microparticles (MPs) and their immune complexes (MPs-ICs) are increased in the circulation of patients with SLE and RA; therefore, we propose these extracellular vesicles could interact and modulate the function of endothelial cells...
January 23, 2019: Arthritis Research & Therapy
Bixia Tang, Xieqiao Yan, Xinan Sheng, Lu Si, Chuanliang Cui, Yan Kong, Lili Mao, Bin Lian, Xue Bai, Xuan Wang, Siming Li, Li Zhou, Jiayi Yu, Jie Dai, Kai Wang, Jinwei Hu, Lihou Dong, Haifeng Song, Hai Wu, Hui Feng, Sheng Yao, Zhihong Chi, Jun Guo
BACKGROUND: JS001, a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor, blocks the interaction of PD-1 with its ligands and promotes T cell activation in preclinical studies. This phase I study is designed to evaluate the safety, tolerability, and clinical activity of JS001 in advanced melanoma or urologic cancer patients who are refractory to standard systemic therapy. PATIENTS AND METHODS: In the dose escalation cohorts, subjects initially received a single-dose, intravenous infusion of JS001, and were followed for 28 days followed by multi-dose infusions every 2 weeks...
January 14, 2019: Journal of Hematology & Oncology
Vahid Bagheri, Mohammad Reza Abbaszadegan, Bahram Memar, Mohammad Reza Motie, Mahdi Asadi, Reihaneh Alsadat Mahmoudian, Mehran Gholamin
Gastric cancer (GC) as the third most common cause of cancer-associated mortality worldwide is one of the cancers with very high heterogeneity. Cancer stem cells (CSCs) as a small subset of cancer cells in solid tumors with the self-renewal, differentiation and tumorigenic ability are responsible for tumor initiation, progression, recurrence, metastasis, and resistance to current treatments. Therefore, eradication of CSCs is very vital to cure cancer. Here, we first isolated and identified sphere-forming cells in tumor tissue from four GC patients and then analyzed T cell responses induced by monocyte-derived dendritic cells (DCs) loaded with total mRNA of sphere-forming cells in terms of interferon-gamma (IFN-γ) gene expression and specific cytotoxicity...
January 11, 2019: Life Sciences
Bor-Ren Huang, Da-Tian Bau, Tzu-Sheng Chen, I-Chen Chuang, Cheng-Fang Tsai, Pei-Chun Chang, Horng-Chaung Hsu, Dah-Yuu Lu
OBJECTIVE: Intervertebral disc (IVD) degeneration and disc herniation are major causes of lower back pain, which involve the presence of inflammatory mediators and tissue invasion by immune cells. Intercellular adhesion molecule 1 (ICAM1, also termed CD54) is an adhesion molecule that mediates cell-cell interactions, particularly between immune cells and target tissue. The aim of this study was to examine the intracellular signaling pathways involved in inflammatory stimuli-induced ICAM1 expression in human anulus fibrosus (AF) cells...
December 25, 2018: International Journal of Molecular Sciences
Christian Peters, Annika Meyer, Léonce Kouakanou, Julia Feder, Tim Schricker, Marcus Lettau, Ottmar Janssen, Daniela Wesch, Dieter Kabelitz
TGF-β is a pleiotropic cytokine with multiple roles in immunity. Apart from its suppressive activity, TGF-β is a driving cytokine in the differentiation of induced regulatory T cells (iTreg) but also in the polarization of interleukin-9 (IL-9) producing T helper 9 (Th9) T cells. Human Vδ2 expressing γδ T cells exert potent cytotoxicity towards a variety of solid tumor and leukemia/lymphoma target cells and thus are in the focus of current strategies to develop cell-based immunotherapies. Here we report that TGF-β unexpectedly augments the cytotoxic effector activity of short-term expanded Vδ2 T cells when purified γδ T cells are activated with specific pyrophosphate antigens and IL-2 or IL-15 in the presence of TGF-β...
2019: Oncoimmunology
Yu A Romanov, N E Volgina, T N Dugina, N V Kabaeva, G T Sukhikh
Production of microvesicles in culture of human umbilical cord multipotent mesenchymal stromal cells was studied and comparative analysis of the expression of some surface molecules (clusters of differentiation, CD) was performed. It was found that the mesenchymal stromal cells produce microvesicles in the amount sufficient for their detection by flow cytometry. Parallel analysis of the phenotypes of maternal mesenchymal stromal cells and secreted microvesicles revealed identical expression of surface molecules CD13, CD29, CD44, CD54, CD71, CD73, CD90, CD105, CD106, and HLA-I...
November 2018: Bulletin of Experimental Biology and Medicine
Jian Zhou, Rong Wu, Long Wang
Objective To observe the effect of panax notoginsenosides (PNS) on cardiac function of rats after acute myocardial infarction (AMI) and investigate the influence of PNS on the mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs). Methods A total of 48 rats were randomly assigned into the sham group, AMI group, low-dose PNS group [100 mg/(kg.d)] and high-dose PNS group [500 mg/(kg.d)]. The rat model of AMI was established by coronary ligation, and 6 rats were sacrificed in each group after 7 and 21 days of treatment with high and low doses of PNS...
July 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Catalina Marín-Echeverri, Juan C Aristizábal, Natalia Gallego-Lopera, Hugo A Santa-Ramírez, Marcela Hoyos-Gómez, Adriana Marcela Ruiz-Pineda, Andrés A Arias, Jacqueline Barona-Acevedo
Background Abdominal obesity (AO) is linked to inflammation and insulin resistance (IR). However, there is limited information on whether preschoolers with AO present these risk factors. We evaluated the association between AO and cardiovascular risk factors in preschoolers. Methods We enrolled 232 children (2-5 years), of whom 50% had AO. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), triglycerides (TG), apolipoprotein B (Apo-B) and apolipoprotein A-1 (Apo-A1), glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, monocyte chemoattractant protein (MCP-1/CCL2), leptin, adiponectin, vascular cell adhesion molecule (VCAM-1/CD106) and intercellular adhesion molecule (ICAM-1/CD54) were measured...
November 27, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
Chathuraka T Jayasuriya, John Twomey-Kozak, Jake Newberry, Salomi Desai, Peter Feltman, Jonathan R Franco, Neill Li, Richard Terek, Michael G Ehrlich, Brett D Owens
Meniscus injuries are among the most common orthopedic injuries. Tears in the inner one-third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized that progenitor cells from healthy human articular cartilage (chondroprogenitor cells [C-PCs]) may be more suitable than bone-marrow mesenchymal stem cells (BM-MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus. C-PCs were isolated from healthy human articular cartilage based on their expression of mesenchymal stem/progenitor marker activated leukocyte cell adhesion molecule (ALCAM) (CD166)...
October 24, 2018: Stem Cells
Juan S Naranjo-Gómez, Andrés Castillo, Mauricio Rojas, Bertha N Restrepo, Francisco J Diaz, Paula A Velilla, Diana Castaño
Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients than in controls...
October 13, 2018: Immunology
Gertrude Ecklu-Mensah, Rebecca W Olsen, Anja Bengtsson, Michael F Ofori, Lars Hviid, Anja T R Jensen, Yvonne Adams
The lack of suitable animal models for the study of cytoadhesion of P. falciparum-infected erythrocytes (IEs) has necessitated in vitro studies employing a range of cell lines of either human tumour origin (e.g., BeWo and C32 cells) or non-human origin (e.g., CHO cells). Of the human cells available, many were isolated from adults, or derived from a pool of donors (e.g., HBEC-5i). Here we demonstrate, for the first time, the successful isolation of blood outgrowth endothelial cells (BOECs) from frozen stabilates of peripheral blood mononuclear cells obtained from small-volume peripheral blood samples from paediatric malaria patients...
2018: PloS One
Ahmed Al-Qaissi, Maria Papageorgiou, Harshal Deshmukh, Leigh A Madden, Alan Rigby, Eric S Kilpatrick, Stephen L Atkin, Thozhukat Sathyapalan
AIMS: To assess whether endothelial microparticles (EMPs), novel surrogate markers of endothelial injury and dysfunction, are differentially produced in response to acute insulin-induced hypoglycaemia in adults with and without type 2 diabetes. MATERIALS AND METHODS: A prospective, parallel study was conducted in individuals with type 2 diabetes (n = 23) and controls (n = 22). Hypoglycaemia (<2.2 mmoL/L: <40 mg/dL) was achieved by intravenous infusion of soluble insulin...
September 28, 2018: Diabetes, Obesity & Metabolism
Xi Chen, Xiaojie Ai, Chunlian Wu, Heyong Wang, Gang Zeng, Peixin Yang, Gentao Liu
IL-2 is critical to the activation, growth, and survival of T cells and NK cells, and maintains the delicate balance between auto-immunity and anti-neoplasm surveillance. High IL-2 doses have clear antitumor capabilities, but also have severe side effects that limit its clinical use. Side effects include the vascular leak syndrome (VLS), which results in lung edema and liver damage. Therefore, a new version of IL-2 that does not induce organ toxicity would improve IL-2-based immunotherapy. We conducted a systematic screening by changing one amino acid at a time at the interaction area of IL-2 with its receptor IL-2R to select one particular mutant IL-2, FSD13, in which the proline at position 65 was substituted by lysine (P65L)...
September 24, 2018: Cell Death & Disease
Erika Moravcikova, E Michael Meyer, Mirko Corselli, Vera S Donnenberg, Albert D Donnenberg
Human culture-expanded mesenchymal stromal cells (MSC) are being considered for multiple therapeutic applications because of their regenerative and anti-inflammatory properties. Although a large number of MSC can be propagated from a small initial sample, several lines of evidence indicate that MSC lose their immunosuppressive and regenerative potency aftaer multiple passages. In this report, we use the FACSCAP Lyoplate proteomic analysis system to detect changes in cell surface protein expression of CD45- /CD31- /CD34- /CD73+ /CD105+ stromal cells in unpassaged bone marrow (BM) and through 10 serial culture passages...
July 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Lisa M Kronstad, Christof Seiler, Rosemary Vergara, Susan P Holmes, Catherine A Blish
In human and murine studies, IFN-γ is a critical mediator immunity to influenza. IFN-γ production is critical for viral clearance and the development of adaptive immune responses, yet excessive production of IFN-γ and other cytokines as part of a cytokine storm is associated with poor outcomes of influenza infection in humans. As NK cells are the main population of lung innate immune cells capable of producing IFN-γ early in infection, we set out to identify the drivers of the human NK cell IFN-γ response to influenza A viruses...
October 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Christian Schwabe, Bernd Rosenstock, Thi Doan, Paul Hamilton, P Rod Dunbar, Anastasia G Eleftheraki, David Joseph, James Hilbert, Corinna Schoelch, Steven J Padula, Jürgen Steffgen
BI 655064 is a humanized antagonistic anti-cluster of differentiation (CD) 40 monoclonal antibody that selectively blocks the CD40-CD40L interaction. The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and lupus nephritis. The safety, tolerability, pharmacokinetics, and pharmacodynamics of repeated once-weekly BI 655064 subcutaneous dosing over 4 weeks were evaluated in a multiple-dose study in healthy subjects. Subjects (N = 40) were randomized 4:1 to four sequential BI 655064 dose groups (80, 120, 180, 240 mg) or to placebo...
August 16, 2018: Journal of Clinical Pharmacology
Marsha S Russell, Abenaya Muralidharan, Louise Larocque, Jingxin Cao, Yvon Deschambault, Jessie Varga, Sathya N Thulasi Raman, Xuguang Li
Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses...
2018: PloS One
Eun-Jung Park, Hong-Soo Lee, Sang Jin Lee, Yoo-Jin Park, Son-Il Park, Jaerak Chang, Kyuhong Lee
Considering that cigarette smoke condensate (CSC) is primarily absorbed through the alveoli in the lungs, herein, we used a mouse alveolar macrophage cell line (MH-S cells). After 24 h exposure, CSC decreased dose-dependently cell viability accompanying an increase in intracellular ROS and NO level. CSC structurally or functionally damaged organelles including mitochondria, ER and lysosome and enhanced the expression of proteins related to apoptosis, ER stress and DNA damage accompanying an elevated proportion of annexin V-bound cells...
October 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Kenneth P Hough, Landon S Wilson, Jennifer L Trevor, John G Strenkowski, Njeri Maina, Young-Il Kim, Marion L Spell, Yong Wang, Diptiman Chanda, Jose Rodriguez Dager, Nirmal S Sharma, Miranda Curtiss, Veena B Antony, Mark T Dransfield, David D Chaplin, Chad Steele, Stephen Barnes, Steven R Duncan, Jeevan K Prasain, Victor J Thannickal, Jessy S Deshane
Asthma is a chronic inflammatory disease process involving the conductive airways of the human lung. The dysregulated inflammatory response in this disease process may involve multiple cell-cell interactions mediated by signaling molecules, including lipid mediators. Extracellular vesicles (EVs) are lipid membrane particles that are now recognized as critical mediators of cell-cell communication. Here, we compared the lipid composition and presence of specific lipid mediators in airway EVs purified from the bronchoalveolar lavage (BAL) fluid of healthy controls and asthmatic subjects with and without second-hand smoke (SHS) exposure...
July 9, 2018: Scientific Reports
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