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Stefan Roepcke, Nele Plock, Josh Yuan, Eric R Fedyk, Gezim Lahu, Lin Zhao, Glennda Smithson
We are studying the fully human, IgG1λ cytolytic monoclonal antibody TAK-079, which binds CD38. CD38 is expressed on plasma and natural killer (NK) cells constitutively and upregulated on subsets of B and T lymphocytes upon activation. TAK-079 cross-reacts with CD38 expressed by cynomolgus monkeys and depletes subsets of NK, B, and T cells. Therefore, safety and function of TAK-079 was evaluated in this species, prior to clinical development, using bioanalytical, and flow cytometry assays. We pooled the data from eight studies in healthy monkeys (dose range 0...
June 2018: Pharmacology Research & Perspectives
Emma M Carrington, David M Tarlinton, Daniel H Gray, Nicholas D Huntington, Yifan Zhan, Andrew M Lew
Targeting survival mechanisms of immune cells may provide an avenue for immune intervention to dampen unwanted responses (e.g. autoimmunity, immunopathology and transplant rejection) or enhance beneficial ones (e.g. immune deficiency, microbial defence and cancer immunotherapy). The selective survival mechanisms of the various immune cell types also avails the possibility of specific tailoring of such interventions. Here, we review the role of the BCL-2 anti-apoptotic family members (BCL-2, BCL-XL, BCL-W, MCL-1 and A1) on cell death/survival of the major immune cell types, for example, T, NK, B, dendritic cell (DC) lineages...
November 2017: Immunology and Cell Biology
Domenico Giordano, Saverio Loddo, Antonio Simone Laganà, Giuseppe Coppolino, Giuseppe Zoccali, Antonino Di Benedetto, Angelo Santamaria, Michele Buemi, Rosario D'Anna
PURPOSE: To evaluate the levels of peripheral blood CD34+  cells in women who subsequently had a spontaneous miscarriage (SM). MATERIALS AND METHODS: We enrolled 11 women who had SM, matching them for age, BMI and gestational age with 33 healthy pregnancies (controls). From a blood sample at 9th-11th weeks of pregnancy, we evaluated PAPP-A, free β-hCG, T (suppressor and helper), NK, B, CD34+  cells. RESULTS: In peripheral blood of women who had SM, PAPP-A and CD34+  cells were significantly lower (p < 0...
January 2018: Journal of Maternal-fetal & Neonatal Medicine
Gabrielle M Siegers, Christy R Barreira, Lynne-Marie Postovit, Gregory A Dekaban
The CD11d integrin is expressed on the cell surface of leukocytes that belong to the myeloid lineage, but its expression on lymphocytes remains unexplored. To test the hypothesis that CD11d is expressed on lymphocyte subsets, we employed a multicolor flow cytometry panel to identify CD11d expression on B, NK, CD4+ and CD8+ αβ T cells (αβTc), and γδ T cells (γδTc) in human PBMC samples. CD11d was highly expressed on NK cells, B cells, and γδTc, but not αβTc. CD11d expression was higher on freshly isolated γδTc compared with αβTc from healthy donors, yet both inter- and intradonor variability was evident...
April 2017: Journal of Leukocyte Biology
R J Kuon, K Vomstein, M Weber, F Müller, C Seitz, S Wallwiener, T Strowitzki, E Schleussner, U R Markert, V Daniel, B Toth
Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to their receptor expression. Recent studies indicate an association of elevated pNK and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK in patients with RM and healthy controls. Out of n=590 RM patients screened according to a standard diagnostic protocol, n=268 couples with ≥3 consecutive RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls...
February 2017: Journal of Reproductive Immunology
Wenjun Mou, Jianxin He, Xi Chen, Hui Zhang, Xiaoya Ren, Xunyao Wu, Xin Ni, Baoping Xu, Jingang Gui
Severe combined immunodeficiency (SCID) is the most serious disorder among primary immunodeficiency diseases threatening children's life. Atypical SCID variant, presenting with mild reduced T cells subsets, is often associated with infection susceptibility but poor clinical diagnosis. The atypical X-SCID patient in the present study showed a mild clinical presentation with a T(low)NK(+)B(+) immunophenotype. The patient has reduced T- cell subpopulations with a subdued thymic output measured by sjTRECs. Further analysis showed that T cells maintained a normal proliferation and a broad Vβ repertoire...
January 2017: Immunogenetics
Ashton Barnett-Vanes, Anna Sharrock, Theofano Eftaxiopoulou, Hari Arora, Warren Macdonald, Anthony M J Bull, Sara M Rankin
BACKGROUND: Understanding of the cellular immune response to primary blast lung injury (PBLI) is limited, with only the neutrophil response well documented. Moreover, its impact on the immune response in distal organs remains poorly understood. In this study, a rodent model of isolated primary blast injury was used to investigate the acute cellular immune response to isolated PBLI in the circulation and lung, including the monocyte response, and investigate distal subacute immune effects in the spleen and liver 6 hours after injury...
September 2016: Journal of Trauma and Acute Care Surgery
Chiang-Wen Lee, Zih-Chan Lin, Lee-Fen Hsu, Jia-You Fang, Yao-Chang Chiang, Ming-Horng Tsai, Ming-Hsueh Lee, Shu-Yu Li, Stephen Chu-Sung Hu, I-Ta Lee, Feng-Lin Yen
ETHNOPHARMACOLOGICAL RELEVANCE: Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved...
August 2, 2016: Journal of Ethnopharmacology
Huilei Cheng, Yanqin Xi, Xianna Chi, Yanxia Wu, Guizhi Liu
OBJECTIVE: To investigate the curative effect of fenofibrate on rats with experimental autoimmune myocarditis (EAM) and its immunological mechanism. MATERIAL AND METHODS: Twenty-four rats were equally randomised into three groups: an EAM group, fenofibrate group, and control group, then a subcutaneous injection of purified pig cardiac myosin was given to the EAM group rats and the fenofibrate group, while equivalent normal saline (NS) was given to the control group...
2016: Central-European Journal of Immunology
Chong Wang, Wenying Long, Chao Peng, Lin Hu, Qiong Zhang, Ailing Wu, Xiaoqing Zhang, Xiaotao Duan, Catherine C L Wong, Yuetsu Tanaka, Zongping Xia
The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events...
April 2016: PLoS Pathogens
Y-T Wang, J-J Fu, X-L Li, Y-R Li, C-F Li, C-Y Zhou
OBJECTIVE: To investigate the effects of hemodialysis (HD) and hemoperfusion (HP) on inflammatory factors and nuclear transcription factors in peripheral blood cell of multiple organ dysfunction syndrome (MODS) patients. PATIENTS AND METHODS: 92 cases of MODS patients undergoing maintained hemodialysis in our hospital were randomly divided into the control group and observation group. The control group was treated with conventional hemodialysis (HD), the observation group was treated with hemoperfusion combined therapy (HD+HP) based on the control group...
2016: European Review for Medical and Pharmacological Sciences
Jing Xu, Fang Zhang, Chao Gao, Xiaofeng Ma, Xiaolin Peng, Dexin Kong, Junwei Hao
For the epigenetic characterization of neuromyelitis optica (NMO), we determined whether messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) are expressed differentially in subjects with and without NMO. lncRNA and mRNA expression profiles of NMO patients and healthy controls were generated by using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated by using gene ontology (GO) and pathway analyses. The microarray revealed that 1310 lncRNAs and 743 mRNAs differed in NMO patients from those in healthy controls...
April 2017: Molecular Neurobiology
Takayuki Murata, Chieko Noda, Yohei Narita, Takahiro Watanabe, Masahiro Yoshida, Keiji Ashio, Yoshitaka Sato, Fumi Goshima, Teru Kanda, Hironori Yoshiyama, Tatsuya Tsurumi, Hiroshi Kimura
UNLABELLED: Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III...
April 2016: Journal of Virology
Sadhna Aggarwal, Satya N Das
Garcinol, a polyisoprenylated benzophenone is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Its ability to inhibit tumour growth has been demonstrated in certain cancers. In this study, we evaluated the potential anti-tumour effects of garcinol on oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines (SCC-4, SCC-9 and SCC-25) were treated with garcinol for 48 h and its effect on growth and proliferation, clonogenic survival, cell cycle and apoptosis was studied by MTT, clonogenic assay, propidium iodide (PI) staining and annexin-V binding assay, respectively...
June 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kyoungran Lee, Joung-Han Yim, Hong-Kum Lee, Suhkneung Pyo
Atherosclerosis is a chronic inflammatory disease, the progression of which is associated with the increased expression of cell adhesion molecules on vascular smooth muscle cells (VSMCs). Lobastin is a new pseudodepsidone isolated from Stereocaulon alpinum, Antarctic lichen, which is known to have antioxidant and antibacterial activities. However, the nature of the biological effects of lobastin still remains unclear. In the present study, we examine the effect of lobastin on the expression of vascular cell adhesion molecules (VCAM-1) induced by TNF-α in the cultured mouse VSMC cell line, MOVAS-1...
January 2016: Archives of Pharmacal Research
Yue Guan, Xiao-Xiao Wu, Jia-Lin Duan, Ying Yin, Chao Guo, Guo Wei, Yan-Hua Wang, Yan-Rong Zhu, Yan Weng, Miao-Miao Xi, Ai-Dong Wen
Traditional Chinese medicine (TCM) plays a systemic role in disease treatment, targeting multiple etiological factors simultaneously. Based on clinical experience, rhubarb and Salvia miltiorrhiza are commonly prescribed together for the treatment of chronic kidney disease (CKD) and have been proven to be very effective. However, the rationale of the combination remains unclear. The major active ingredients of these two herbs are rhein (RH) and danshensu (DSS), respectively. The aim of this paper is to investigate the renoprotective effects of RH and DSS in vitro and in vivo, and the underlying mechanism...
2015: American Journal of Chinese Medicine
Y Liao, K-H Chen, X-M Dong, Y Fang, W-G Li, G-Y Huang, W Song
OBJECTIVE: Acute viral myocarditis (VM) is an important cause of sudden cardiac death and heart failure in healthy young person. Direct virus-mediated injury and secondary immune reactions, including inflammatory and autoimmune responses, have been reported both in animal models and in humans. Recently, genetic variation has been confirmed related to myocarditis process and susceptibility to VM. In this study, we scanned 339bp of pri-miR-10a coding region in CVB3 VM patients, want to found genetic relations between miR-10a and VM susceptibility...
September 2015: European Review for Medical and Pharmacological Sciences
Weiping Tan, Sifei Yu, Jiaying Lei, Baojing Wu, Changyou Wu
X-linked severe combined immunodeficiency (X-SCID) is one of the most common causes of primary immunodeficiencies in humans. A 4-month-old boy with recurrent pulmonary infection had decreased numbers of CD3(+), CD4(+), CD8(+) T lymphocytes, and NK cells and increased levels of CD19(+) B cells but no memory B cells or plasma cells. The production of cytokines by T cells and the activation of T and B cells were either absent or inefficient. While B cell levels were high, they were all IgM-positive, and the secretion of all Ig isotypes by activated B cells in vitro was defective...
November 2015: Immunogenetics
Z Lee, S Nishikawa, S Gao, J B Eksteen, M Czub, M J Gill, C Osiowy, F van der Meer, G van Marle, C S Coffin
UNLABELLED: The hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1) can infect cells of the lymphatic system. It is unknown whether HIV-1 co-infection impacts infection of peripheral blood mononuclear cell (PBMC) subsets by the HBV. AIMS: To compare the detection of HBV genomes and HBV sequences in unsorted PBMCs and subsets (i.e., CD4+ T, CD8+ T, CD14+ monocytes, CD19+ B, CD56+ NK cells) in HBV mono-infected vs. HBV/HIV-1 co-infected individuals...
2015: PloS One
Immo Prinz, Inga Sandrock
The term immunological memory has long been a trademark restricted to adaptive lymphocytes such as memory B cells and plasma cells as well as memory CD8(+) αβ T cells. In recent years, innate lymphocytes such as NK cells have also been shown to adapt to their environment by antigen-specific expansion and selective survival. However, whether γδ T cells mount comparable memory responses to pathogenic stimuli is less well understood. In this issue of European Journal of Immunology, Hartwig et al. [Eur. J. Immunol...
November 2015: European Journal of Immunology
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