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KIR type

Ashley Moffett, Olympe Chazara, Francesco Colucci, Martin H Johnson
A distinctive type of (uterine) natural killer (NK) cell is present in the uterine decidua during the period of placental formation. Uterine NK cells express members of the killer immunoglobulin-like receptor (KIR) family that bind to parental HLA-C molecules on the invading placental trophoblast cells. The maternal KIR genes and their fetal ligands are highly variable, so different KIR/HLA-C genetic combinations occur in each pregnancy. Some women only possess inhibitory KIR genes, whereas other women also express activating KIR genes...
September 5, 2016: Reproductive Biomedicine Online
Cynthia Vierra-Green, David Roe, Jyothi Jayaraman, John Trowsdale, James Traherne, Rui Kuang, Stephen Spellman, Martin Maiers
The killer cell immunoglobulin-like receptors (KIR) mediate human natural killer (NK) cell cytotoxicity via activating or inhibiting signals. Although informative and functional haplotype patterns have been reported, most genotyping has been performed at resolutions that are structurally ambiguous. In order to leverage structural information given low-resolution genotypes, we performed experiments to quantify the effects of population variations, reference haplotypes, and genotyping resolutions on population-level haplotype frequency estimations as well as predictions of individual haplotypes...
2016: PloS One
Daniele Kazue Sugioka, Carlos Eduardo Ibaldo Gonçalves, Maria da Graça Bicalho
BACKGROUND: Since the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant...
2016: BMC Hematology
B Erer, M Takeuchi, D Ustek, I Tugal-Tutkun, E Seyahi, Y Özyazgan, J Duymaz-Tozkir, A Gül, D L Kastner, E F Remmers, M J Ombrello
The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors...
October 6, 2016: Genes and Immunity
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
October 3, 2016: Glia
W Jiang, C Johnson, N Simecek, M R López-Álvarez, D Di, J Trowsdale, J A Traherne
Killer cell immunoglobulin-like receptors (KIRs), expressed on natural killer cells and T cells, have considerable biomedical relevance playing significant roles in immunity, pregnancy and transplantation. The KIR locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes KIRs technically laborious and expensive to type. To aid the investigation of KIRs in human disease we developed a high-throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each KIR locus...
September 29, 2016: Genome Medicine
Enzo Wanke, Francesca Gullo, Elena Dossi, Gaetano Valenza, Andrea Becchetti
Astrocytes reuptake synaptically released glutamate with electrogenic transporters (GluT), and buffer the spike-dependent extracellular K(+) ([K(+)]o) excess with background K(+) channels. We studied neuronal spikes and the slower astrocytic signals on reverberating neocortical cultures and organotypic slices from mouse brains. Spike trains and glial responses were simultaneously captured from individual sites of multi-electrode arrays (MEA), by splitting the recorded traces into appropriate filters, and reconstructing the original signal by deconvolution...
September 28, 2016: Journal of Neurophysiology
Hisham A Edinur, Siti M Manaf, Nor F Che Mat
The successful of transplantation is determined by the shared human leukocyte antigens (HLAs) and ABO blood group antigens between donor and recipient. In recent years, killer cell receptor [i.e., killer cell immunoglobulin-like receptor (KIR)] and major histocompatibility complex (MHC) class I chain-related gene molecule (i.e., MICA) were also reported as important determinants of transplant compatibility. At present, several different genotyping techniques (e.g., sequence specific primer and sequence based typing) can be used to characterize blood group, HLA, MICA and KIR and loci...
September 24, 2016: World Journal of Transplantation
Mariella Della Chiesa, Silvia Pesce, Letizia Muccio, Simona Carlomagno, Simona Sivori, Alessandro Moretta, Emanuela Marcenaro
Human NK cells are distinguished into CD56(bright)CD16(-) cells and CD56(dim)CD16(+) cells. These two subsets are conventionally associated with differential functional outcomes and are heterogeneous with respect to the expression of KIR and CD94/NKG2 heterodimers that represent the two major types of HLA-class I-specific receptors. Recent studies indicated that immature CD56(bright) NK cells, homogeneously expressing the inhibitory CD94/NKG2A receptor, are precursors of CD56(dim) NK cells that, in turn, during their process of differentiation, lose expression of CD94/NKG2A and subsequentially acquire inhibitory KIRs and LIR-1...
2016: Frontiers in Immunology
Suliman Y Alomar, Afrah Alkhuriji, Paul Trayhyrn, Abdulkarim Alhetheel, Abdullah Al-Jurayyan, Lamjed Mansour
Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women...
September 15, 2016: Immunogenetics
Marion Depla, Sandy Pelletier, Nathalie Bédard, Camille Brunaud, Julie Bruneau, Naglaa H Shoukry
INTRODUCTION: Polymorphisms in the type III interferon IFN-λ3 and the killer cell immunoglobulin-like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN-λ3 polymorphism may modulate NK cell function during acute HCV. METHODS: We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes...
September 2016: Immunity, Inflammation and Disease
V Kazanski, V M Mitrokhin, M I Mladenov, A G Kamkin
: The role of cytokines as regulators of stretch-related mechanisms is of special importance since mechano-sensitivity plays an important role in a wide variety of biological processes. Here, we elucidate the influence of cytokine application on mechano-sensitivity and mechano-transduction. The atrial myocardial stretch induces production of interleukin (IL)-2, IL-6, IL-13, IL-17A, and IL-18 with exception of tumor necrosis factor α (TNF-α), IL-1β, and vascular endothelial growth factor B (VEGF-B)...
September 12, 2016: Immunological Investigations
Ge Sun, Chang Wang, Jianxin Zhen, Guobin Zhang, Yunping Xu, Zhihui Deng
OBJECTIVE: To develop an assay for cDNA cloning and haplotype sequencing of KIR2DL1 framework gene and determine the genotype of an ethnic Han from southern China. METHODS: Total RNA was isolated from peripheral blood sample, and complementary DNA (cDNA) transcript was synthesized by RT-PCR. The entire coding sequence of the KIR2DL1 framework gene was amplified with a pair of KIR2DL1-specific PCR primers. The PCR products with a length of approximately 1.2 kb were then subjected to cloning and haplotype sequencing...
October 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Alice Goode, Sarah Rea, Melanie Sultana, Barry Shaw, Mark S Searle, Robert Layfield
The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of neurodegenerative disorders. The Keap1-binding partner and autophagy receptor SQSTM1/p62 has also recently been linked genetically to ALS-FTLD, with some missense mutations identified in patients mapping within or close to its Keap1-interacting region (KIR, residues 347-352)...
October 2016: Molecular and Cellular Neurosciences
Angelica Canossi, Anna Aureli, Tiziana Del Beato, Piero Rossi, Luana Franceschilli, Flavio De Sanctis, Pierpaolo Sileri, Nicola di Lorenzo, Oreste Buonomo, Davide Lauro, Adriano Venditti, Giuseppe Sconocchia
BACKGROUND: NK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells...
2016: Journal of Translational Medicine
Ralph D Levinson, Madeline Yung, Akira Meguro, Elham Ashouri, Fei Yu, Nobuhisa Mizuki, Shigeaki Ohno, Raja Rajalingam
Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility...
2016: PloS One
Francesca Rusconi, Paola Ceriotti, Michele Miragoli, Pierluigi Carullo, Nicolò Salvarani, Marcella Rocchetti, Elisa Di Pasquale, Stefano Rossi, Maddalena Tessari, Silvia Caprari, Magali Cazade, Paolo Kunderfranco, Jean Chemin, Marie-Louise Bang, Fabio Polticelli, Antonio Zaza, Giuseppe Faggian, Gianluigi Condorelli, Daniele Catalucci
BACKGROUND: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease. METHODS: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Cavβ2 chaperone regulates channel density at the plasma membrane...
August 16, 2016: Circulation
Danillo G Augusto
The polymorphism of killer cell immunoglobulin-like receptors (KIR) has been associated with several diseases, including infection, autoimmunity and cancer. KIR molecules are a family of receptors expressed on the surface of natural killer cells (NK), frontline defense of innate immunity against microorganisms and neoplastic cells. Some studies have shown conflicting results concerning the role that KIR polymorphism plays in tumor susceptibility, particularly in leukemia and lymphoma. Interestingly, the presence of HLA ligands is sometimes strongly associated with several types of cancer and apparently is not related with their interaction with KIR...
2016: Frontiers in Genetics
Meriç Kaymak Cihan, Olcay Kandemir, Klara Dalva, Neriman Sarı, Nilgün Kurucu, İnci Ergürhan İlhan
Familial clustering of Hodgkin lymphoma (HL) and increased risk of developing disease among the siblings has been reported earlier. Usually familial lymphoma in sibling pairs occurs in the pairs of either non-Hodgkin lymphoma or HL. In the familial HL, same type of human leukocyte antigens (HLA) is responsible in the affected family members. There are also some studies stating "Killer cell immunoglobulin like receptor (KIR)" genotypes can be important in the etiology of familial HL. Here we report two siblings; one with Non-Hodgkin and the other with Hodgkin lymphoma which showed Epstein-Barr virus encoded small RNAs positivity in the tumor tissues...
September 2015: Turkish Journal of Pediatrics
M Joskova, M Sutovska, P Durdik, D Koniar, L Hargas, P Banovcin, M Hrianka, V Khazaei, L Pappova, S Franova
Overproduction of mucus is a hallmark of asthma. The aim of this study was to identify potentially effective therapies for removing excess mucus. The role of voltage-gated (Kir 6.1, KCa 1.1) and store-operated ion channels (SOC, CRAC) in respiratory cilia, relating to the tracheal ciliary beat frequency (CBF), was compared under the physiological and allergic airway conditions. Ex vivo experiments were designed to test the local effects of Kir 6.1, KCa 1.1 and CRAC ion channel modulators in a concentration-dependent manner on the CBF...
2016: Advances in Experimental Medicine and Biology
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