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https://www.readbyqxmd.com/read/28098874/mica-il-12-a-novel-bifunctional-protein-for-killer-cell-activation
#1
Ashlee Tietje, Xi Yang, Xianzhong Yu, Yanzhang Wei
Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors such as NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce the expression of these ligands, leaving them less detectable by NK cells. Along with these receptors, NK cells also require activating cytokines, such as IL-12. A previous study in our laboratory showed that a fusion protein of the extracellular domain of mouse UL-16 binding protein-like transcript 1 (MULT1E) and mouse interleukin 12 (IL-12) can effectively activate mouse NK cells by in vitro assays and in vivo in animal tumor models...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098245/natural-cytotoxicity-receptor-1-in-mouse-unk-cell-maturation-and-function
#2
A M Felker, B A Croy
Early and midgestational decidua of mice genetically ablated for expression of the natural killer (NK) cell natural cytotoxicity receptor (NCR; Ncr1(Gfp/Gfp) mice) shows restricted angiogenesis and atypically small uterine (u)NK cells . We hypothesized that NCR1 inactivation disturbs maturation and angiokine production by uterine natural killer (uNK) cells. Using histological and morphometric approaches, we observed that Ncr1(Gfp/Gfp) but not control C57BL/6 (B6) implantation sites sustain immature, non-granulated uNK cells into midpregnancy...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28097463/neurokinin-1-receptor-immunopositive-neurons-in-the-medullary-dorsal-horn-provide-collateral-axons-to-both-the-thalamus-and-parabrachial-nucleus-in-rats
#3
Xu Li, Shun-Nan Ge, Yang Li, Han-Tao Wang
It has been suggested that the trigemino-thalamic and trigemino-parabrachial projection neurons in the medullary dorsal horn (MDH) are highly implicated in the sensory-discriminative and emotional/affective aspects of orofacial pain, respectively. In previous studies, some neurons were reported to send projections to both the thalamus and parabrachial nucleus by way of collaterals in the MDH. However, little is known about the chemoarchitecture of this group of neurons. Thus, in the present study, we determined whether the neurokinin-1 (NK-1) receptor, which is crucial for primary orofacial pain signaling, was expressed in MDH neurons co-innervating the thalamus and parabrachial nucleus...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28097229/anti-sirp%C3%AE-antibodies-as-a-potential-new-tool-for-cancer-immunotherapy
#4
Tadahiko Yanagita, Yoji Murata, Daisuke Tanaka, Sei-Ichiro Motegi, Eri Arai, Edwin Widyanto Daniwijaya, Daisuke Hazama, Ken Washio, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Per-Arne Oldenborg, Noel Verjan Garcia, Masayuki Miyasaka, Osamu Ishikawa, Yae Kanai, Takahide Komori, Takashi Matozaki
Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096659/effects-of-multiple-dose-ponesimod-a-selective-s1p1-receptor-modulator-on-lymphocyte-subsets-in-healthy-humans
#5
Stipo Jurcevic, Pierre-Eric Juif, Colleen Hamid, Roseanna Greenlaw, Daniele D'Ambrosio, Jasper Dingemanse
This study investigated the effects of ponesimod, a selective S1P1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days) or placebo (ratio 3:1). The overall change from baseline in lymphocyte count was -1,292±340×10(6) cells/L and 275±486×10(6) cells/L in ponesimod- and placebo-treated subjects, respectively...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28095504/cytoplasmic-localization-of-htlv-1-hbz-protein-a-biomarker-of-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp
#6
Marco Baratella, Greta Forlani, Goutham U Raval, Alessandra Tedeschi, Olivier Gout, Antoine Gessain, Giovanna Tosi, Roberto S Accolla
HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL), and of a chronic progressive neuromyelopathy designated HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Two important HTLV-1-encoded proteins, Tax-1 and HBZ, play crucial roles in the generation and maintenance of the oncogenic process. Less information is instead available on the molecular and cellular mechanisms leading to HAM/TSP. More importantly, no single specific biomarker has been described that unambiguously define the status of HAM/TSP...
January 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28093832/il-15-deficient-mice-develop-enhanced-allergic-responses-to-airway-allergen-exposure
#7
Clinton B Mathias, Craig M Schramm, Linda A Guernsey, Carol A Wu, Stephanie H Polukort, Jeffrey Rovatti, Jennifer Ser-Dolansky, Eric Secor, Sallie S Schneider, Roger S Thrall, Hector L Aguila
BACKGROUND: Interleukin-15 is a pleiotropic cytokine that is critical for the development and survival of multiple hematopoietic lineages. Mice lacking IL-15 have selective defects in populations of several pro-allergic immune cells including natural killer (NK) cells, NKT cells, and memory CD8(+) T cells. We therefore hypothesized that IL-15(-/-) mice will have reduced inflammatory responses during the development of allergic airway disease (AAD). OBJECTIVE: To determine whether IL-15(-/-) mice have attenuated allergic responses in a mouse model of AAD...
January 17, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28093691/middle-age-enhances-expression-of-innate-immunity-genes-in-a-female-mouse-model-of-pulmonary-fibrosis
#8
Marcin Golec, Matthias Wielscher, Marta Kinga Lemieszek, Klemens Vierlinger, Czesława Skórska, Sophia Huetter, Jolanta Sitkowska, Barbara Mackiewicz, Anna Góra-Florek, Rolf Ziesche, Hagai Yanai, Vadim E Fraifeld, Janusz Milanowski, Jacek Dutkiewicz
The lungs are highly sensitive to tissue fibrosis, with a clear age-related component. Among the possible triggers of pulmonary fibrosis are repeated inhalations of fine organic particles. How age affects this response, is still far from being fully understood. We examined the impact of middle-age on gene expression in pulmonary fibrosis, using the novel "inhalation challenge set" mouse model. Our results demonstrate that the response of female mice to exposure of Pantoea agglomerans extract primarily involves various immune-related pathways and cell-cell/cell-extracellular matrix interactions...
January 16, 2017: Biogerontology
https://www.readbyqxmd.com/read/28093522/cutting-edge-human-cd49e-nk-cells-are-tissue-resident-in-the-liver
#9
Han Xian Aw Yeang, Sytse J Piersma, Yiing Lin, Liping Yang, Olga N Malkova, Cathrine Miner, Alexander S Krupnick, William C Chapman, Wayne M Yokoyama
Most knowledge on NK cells is based on studies of what are now known as conventional NK cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared with conventional NK cells. In this study, we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e(-) NK cells are tissue resident in the liver...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093337/nk-cell-phenotypic-and-functional-shifts-coincide-with-specific-clinical-phases-in-the-natural-history-of-chronic-hbv-infection
#10
Rik A de Groen, Jun Hou, Gertine W van Oord, Zwier M A Groothuismink, Marieke van der Heide, Robert J de Knegt, André Boonstra
BACKGROUND: Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. METHODS: Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells...
January 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28093266/comparative-analysis-of-nk-cell-receptor-repertoire-in-adults-and-very-elderly-subjects-with-cytomegalovirus-infection
#11
Guillermo Juárez-Vega, Velia Rangel-Ramírez, Adriana Monsiváis-Urenda, Perla Niño-Moreno, Christian Garcia-Sepúlveda, Daniel E Noyola, Roberto González-Amaro
Human cytomegalovirus (HCMV) infection in children and young adults has been associated with changes in the innate immune system. We herein analyzed the possible effect of very long term HCMV infection on the expression of several NK cell receptors. Ninety HCMV-seropositive individuals were included and classified as young adults (n=30), elderly (n=30) and very elderly subjects (n=30). A peripheral blood sample was obtained and the expression of NK cell receptors (NKG2A, NKG2C, ILT2, CD161, KIR2DL1, KIR3DL1, and KIR3DL2) by NK and other lymphocyte subsets was assessed by flow cytometry...
January 13, 2017: Human Immunology
https://www.readbyqxmd.com/read/28092804/enhancement-of-nk-cell-mediated-lysis-of-non-small-lung-cancer-cells-by-npkc-activator-ingenol-3-20-dibenzoate
#12
Chenyuan Gong, Chao Yao, Zihang Xu, Zhongya Ni, Xiaowen Zhu, Lixin Wang, Xuewei Yan, Wuxiong Zhou, Shiguo Zhu
The IFN-γ production is crucial for NK cell-mediated lysis of cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards natural products, limited information is out there about natural products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung cancer (NSCLC) cells...
January 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-il-23-mediated-protection-against-cona-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#13
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδT cells and liver damage in patients with HBV. However, whether γδT cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using hepatitis B virus transgenic (HBs-Tg) and HBs-Tg-TCRδ(-/-) mice, we found that mice genetically deficient in γδT cells exhibited more severe liver damage upon ConcanavalinA (ConA) treatment, as indicated by substantially higher serum alanine aminotransferase (ALT) levels, further elevated IFN-γ levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#14
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28090599/mas-related-g-protein-coupled-receptor-x2-a-potential-new-target-for-modulating-mast-cell-mediated-allergic-and-inflammatory-diseases
#15
Hydar Ali
Mast cells (MCs) are tissue resident immune cells that are best known for their roles in allergic and inflammatory diseases. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the most common targets of drug therapy. Neurokinin 1 receptor (NK-1R) is expressed on MCs and contributes to IgE and non-IgE-mediated responses in mice. Although NK-1R antagonists are highly effective in modulating experimental allergic and inflammatory responses in mice they lack efficacy in humans...
December 2016: Journal of Immunobiology
https://www.readbyqxmd.com/read/28089340/activation-of-nk-cell-cytotoxicity-by-aerosolized-cpg-odn-poly-i-c-against-lung-melanoma-metastases-is-mediated-by-alveolar-macrophages
#16
Michele Sommariva, Valentino Le Noci, Chiara Storti, Francesca Bianchi, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Controversies remain about NK cells direct responsiveness to Toll-like receptor (TLR) agonists or dependence on macrophages. In a melanoma lung metastasis model, aerosolized TLR9 and TLR3 agonists have been reported to induce antitumor immunity through NK cells activation. In the current study, we demonstrated that in vitro TLR9/TLR3 stimulation induced IFN-γ secretion by NK cells, but an increase in their cytotoxicity was detected only after NK cells co-culture with in vitro TLR9/TLR3 agonists pretreated alveolar macrophages...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28089218/nkg2d-signaling-the-immune-subversive-side-of-hdac3
#17
Alicia R Folgueras, Segundo Gonzalez, Alejandro López-Soto
Natural killer (NK) cells are alerted to infected and transformed cells by local upregulation of ligands for the NK-activating receptor NKG2D. In a recent report, Greene et al. unveil a new mechanism that induces the expression of the NKG2D ligand retinoic acid early-inducible (RAE-1) in response to murine cytomegalovirus (MCMV) infection through inhibition of casein kinase 2 (CK2), an activator of the repressor histone deacetylase HDAC3.
January 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28088979/-value-of-pet-ct-clinical-application-in-extranodal-nk-t-cell-lymphoma
#18
S R Yang, X L Lan
No abstract text is available yet for this article.
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088386/trypsin-induces-biphasic-muscle-contraction-and-relaxation-via-transient-receptor-potential-vanilloid-1-and-neurokinin-receptors-1-2-in-porcine-esophageal-body
#19
Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura
Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088355/kir-genes-and-hla-class-i-ligands-in-a-caucasian-brazilian-population-with-colorectal-cancer
#20
Pâmela Portela, Joice Merzoni, Juliana D Lindenau, Daniel C Damin, Timothy John Wilson, Rafael Roesler, Gilberto Schwartsmann, Luiz Mariana Fernando Jobim Jobim
Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls...
January 11, 2017: Human Immunology
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