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https://www.readbyqxmd.com/read/28630062/the-transcription-factor-nfat1-participates-in-the-induction-of-cd4-t-cell-functional-exhaustion-during-plasmodium-yoelii-infection
#1
Rachel Y Ames, Li-Min Ting, Inessa Gendlina, Kami Kim, Fernando Macian
Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and up-regulate cell-surface inhibitory molecules such as PD-1 and LAG-3...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28617945/microrna-cluster-106a-363-is-involved-in-t-helper-17-th17-cell-differentiation
#2
Marc Kaestle, Sabine Bartel, Kerstin Geillinger-Kästle, Martin Irmler, Johannes Beckers, Bernhard Ryffel, Oliver Eickelberg, Susanne Krauss-Etschmann
T-helper cell 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct Th subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signaling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine Th cell differentiation by combining Affymetrix mRNA and miRNA arrays and in-silico analysis...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28615692/wnt5a-is-associated-with-right-ventricular-dysfunction-and-adverse-outcome-in-dilated-cardiomyopathy
#3
Aurelija Abraityte, Ida G Lunde, Erik T Askevold, Annika E Michelsen, Geir Christensen, Pål Aukrust, Arne Yndestad, Arnt Fiane, Arne Andreassen, Svend Aakhus, Christen P Dahl, Lars Gullestad, Kaspar Broch, Thor Ueland
The Wingless (Wnt) pathway has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). To explore the role of Wnt modulators Wnt5a and sFRP3 in DCM patients we analyzed the expression of Wnt5a and sFRP3 in plasma and myocardium of DCM patients and evaluated their effects on NFAT luciferase activity in neonatal mouse cardiomyocytes. Elevated circulating Wnt5a (n = 102) was associated with increased pulmonary artery pressures, decreased right ventricular function and adverse outcome, with a stronger association in more severely affected patients...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615414/loss-of-ip3-receptor-mediated-ca-2-release-in-mouse-b-cells-results-in-abnormal-b-cell-development-and-function
#4
Huayuan Tang, Hong Wang, Qingsong Lin, Feifei Fan, Fei Zhang, Xiaohong Peng, Xi Fang, Jie Liu, Kunfu Ouyang
Intracellular calcium (Ca(2+)) mobilization after engagement of the BCR has been proposed to play an important role in B cell development and function. BCR activation causes an initial Ca(2+) release from the endoplasmic reticulum that is mediated by inositol 1,4,5-trisphosphate receptor (IP3R) and then triggers store-operated Ca(2+) entry once endoplasmic reticulum Ca(2+) store is depleted. Store-operated Ca(2+) entry has been shown to regulate B cell function but is dispensable for B cell development. By contrast, the function of IP3R-mediated Ca(2+) release in B cells remains to be determined...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28611128/decreased-kcne2-expression-participates-in-the-development-of-cardiac-hypertrophy-by-regulation-of-calcineurin-nfat-nuclear-factor-of-activated-t-cells-and-mitogen-activated-protein-kinase-pathways
#5
Wenjuan Liu, Jianxin Deng, Wenwen Ding, Gang Wang, Yuanyuan Shen, Junmeng Zheng, Xiaoming Zhang, Yizhi Luo, Chifei Lv, Yonghui Wang, Liqing Chen, Dewen Yan, Ryan L Boudreau, Long-Sheng Song, Jie Liu
BACKGROUND: KCNE2 is a promiscuous auxiliary subunit of voltage-gated cation channels. A recent work demonstrated that KCNE2 regulates L-type Ca(2+) channels. Given the important roles of altered Ca(2+) signaling in structural and functional remodeling in diseased hearts, this study investigated whether KCNE2 participates in the development of pathological hypertrophy. METHODS AND RESULTS: We found that cardiac KCNE2 expression was significantly decreased in phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes and in transverse aortic constriction-induced cardiac hypertrophy in mice, as well as in dilated cardiomyopathy in human...
June 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28608562/t11ts-immunotherapy-repairs-pi3k-akt-signaling-in-t-cells-clues-towards-enhanced-t-cell-survival-in-rat-glioma-model
#6
Suhnrita Chaudhuri, Manoj Kumar Singh, Debanjan Bhattacharya, Ankur Datta, Iman Hazra, Somnath Mondal, Omar Faruk Sk Md, Larance Ronsard, Tushar Kanti Ghosh, Swapna Chaudhuri
Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats...
June 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28606994/calcineurin-nfat-signalling-in-myeloid-leucocytes-new-prospects-and-pitfalls-in-immunosuppressive-therapy
#7
REVIEW
Kamila Bendickova, Federico Tidu, Jan Fric
Myeloid leucocytes mediate host protection against infection and critically regulate inflammatory responses in body tissues. Pattern recognition receptor signalling is crucial for myeloid cell responses to pathogens, but growing evidence suggests an equally potent role for Calcineurin-NFAT signalling in control of myeloid cell function. All major subsets of myeloid leucocytes employ Calcineurin-NFAT signalling during immune responses to pathogens and/or tissue damage, but the influence this pathway exerts on pathogen clearance and host susceptibility to infection is not fully understood...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28596584/rcan-11r-peptide-provides-immunosuppression-for-fully-mismatched-islet-allografts-in-mice
#8
Hirofumi Noguchi, Koji Sugimoto, Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi
Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595951/sumoylation-regulates-the-transcriptional-activity-of-different-human-nfat-isoforms-in-neurons
#9
Hanna Vihma, Tõnis Timmusk
In the nervous system, four calcium/calcineurin-regulated members of the nuclear factor of activated T-cells (NFAT) family of transcription factors, NFATc1-c4, are involved in many developmental and functional processes, such as corticogenesis, synaptogenesis, synaptic plasticity and neurotransmission, that all need precise gene regulation. Therefore it is important to understand molecular events that contribute to the regulation of the transcriptional activity of specific NFAT isoforms. Previously, we have shown that there are a number of alternative splice variants of NFAT genes expressed in the brain and that neuronal activity leads to isoform-specific transactivation capacities of different human NFAT proteins...
June 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28594115/therapeutic-relevance-of-ozone-therapy-in-degenerative-diseases-focus-on-diabetes-and-spinal-pain
#10
REVIEW
Nady Braidy, Morteza Izadi, Antoni Sureda, Nematollah Jonaidi-Jafari, Abdolali Banki, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses...
June 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28592414/effects-of-sarcolipin-deletion-on-skeletal-muscle-adaptive-responses-to-functional-overload-and-unload
#11
Val A Fajardo, Bradley A Rietze, Paige J Chambers, Catherine Bellissimo, Eric Bombardier, Joe Quadrilatero, A Russell Tupling
Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses we performed soleus and gastrocnemius tenotomy in wild-type (WT) and Sln¬-null (Sln(-/-)) mice and examined the overloaded plantaris and unloaded/tenotomized soleus muscles...
June 7, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28589943/the-signalling-receptor-mcam-coordinates-apical-basal-polarity-and-planar-cell-polarity-during-morphogenesis
#12
Qian Gao, Junfeng Zhang, Xiumei Wang, Ying Liu, Rongqiao He, Xingfeng Liu, Fei Wang, Jing Feng, Dongling Yang, Zhaoqing Wang, Anming Meng, Xiyun Yan
The apical-basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28584086/il-2-therapy-restores-regulatory-t-cell-dysfunction-induced-by-calcineurin-inhibitors
#13
Gavin Whitehouse, Elizabeth Gray, Sotiris Mastoridis, Elliot Merritt, Elisavet Kodela, Jennie H M Yang, Richard Danger, Marta Mairal, Sofia Christakoudi, Juan J Lozano, Iain C Macdougall, Timothy I M Tree, Alberto Sanchez-Fueyo, Marc Martinez-Llordella
CD4(+)CD25(+)FOXP3(+) Tregs constitute a heterogeneous lymphocyte subpopulation essential for curtailing effector T cells and establishing peripheral tolerance. Calcineurin inhibitors (CNIs) are among the most effective agents in controlling effector T-cell responses in humans. However, CNIs also reduce the size of the Treg pool. The functional consequences of this negative effect and the mechanisms responsible remain to be elucidated. We report here that CNIs compromise the overall Treg immunoregulatory capacity to a greater extent than would be predicted by the reduction in the size of the Treg compartment, given that they selectively promote the apoptosis of the resting and activated Treg subsets that are known to display the most powerful suppressive function...
June 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28560440/the-protective-effects-of-pcpa-against-monocrotaline-induced-pulmonary-arterial-hypertension-are-mediated-through-the-downregulation-of-nfat-1-and-nf-%C3%AE%C2%BAb
#14
Yang Bai, Zhong-Xia Li, Huai-Liang Wang, Guo-Chao Lian, Yun Wang
Inflammation and remodeling play a role in the pathogenesis of pulmonary arterial hypertension (PAH). Nuclear factor-κB (NF-κB) and nuclear factor of activated T cells-1 (NFAT-1) participate in inflammation and remodeling in a number of diseases. As a tryptophan hydroxylase inhibitor, 4-chloro-DL-phenylalanine (PCPA) had been reported to exert anti-inflammatory and remodeling effects. Therefore, we hypothesized that PCPA may attenuate monocrotaline (MCT)-induced PAH through the NFAT-1 and NF-κB signaling pathways...
May 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28559377/calcineurin-nfat-signaling-in-activated-astrocytes-drives-network-hyperexcitability-in-a%C3%AE-bearing-mice
#15
Pradoldej Sompol, Jennifer L Furman, Melanie M Pleiss, Susan D Kraner, Irina A Artiushin, Seth R Batten, Jorge E Quintero, Linda A Simmerman, Tina L Beckett, Mark A Lovell, M Paul Murphy, Greg A Gerhardt, Christopher M Norris
Hyperexcitable neuronal networks are mechanistically-linked to the pathologic and clinical features of Alzheimer's disease (AD). Astrocytes are a primary defense against hyperexcitability, but their functional phenotype during AD is poorly understood. Here, we found that activated astrocytes in the 5xFAD mouse model were strongly associated with proteolysis of the protein phosphatase calcineurin (CN), and the elevated expression of the CN-dependent transcription factor, NFAT4. Intrahippocampal injections of AAV vectors containing the astrocyte specific promoter, Gfa2, and the NFAT inhibitory peptide, VIVIT, reduced signs of glutamate-mediated hyperexcitability in 5xFAD mice, measured in vivo with microelectrode arrays (MEA) and ex vivo brain slices, using whole-cell voltage clamp...
May 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28549244/ll-37-induced-human-mast-cell-activation-through-g-protein-coupled-receptor-mrgx2
#16
Yangyang Yu, Yuanyuan Zhang, Yarui Zhang, Yihong Lai, Wenwen Chen, Zhangang Xiao, Wei Zhang, Meiling Jin, Bo Yu
Human LL-37 is an important class of cationic antimicrobial peptide (CAP) that is known to stimulate mast cell activation. While many studies have been conducted on LL-37, to date little is known about the functional receptors for LL-37-induced human mast cell activation, in particular in terms of the release of de novo synthesized mediators. Thus, the aim of the present study is to identify the functional receptors for LL-37-induced human mast cell activation in terms of the degranulation and release of de novo synthesized mediators and investigate the downstream signalling pathways involved in mast cell activation...
May 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28539593/identification-of-the-matricellular-protein-fibulin-5-as-a-target-molecule-of-glucokinase-mediated-calcineurin-nfat-signaling-in-pancreatic-islets
#17
Tomoko Okuyama, Jun Shirakawa, Hiromi Yanagisawa, Mayu Kyohara, Shunsuke Yamazaki, Kazuki Tajima, Yu Togashi, Yasuo Terauchi
Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#18
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28526484/regulation-of-cacybp-sip-expression-by-nfat1-transcription-factor
#19
Beata Kądziołka, Wiesława Leśniak, Anna Filipek
In this work we have shown that NFAT1 transcription factor is involved in the regulation of CacyBP/SIP expression. We have demonstrated, by applying Western blot, RT-PCR and luciferase assay that the level of CacyBP/SIP increases upon NFAT1 overexpression. Moreover, inhibition or stimulation of NFAT transcriptional activity exerts a corresponding effect on the expression of CacyBP/SIP gene. Furthermore, EMSA and chromatin immunoprecipitation (ChIP) assay have shown that NFAT1 binds to its specific binding sites within the CacyBP/SIP gene...
August 2017: Immunobiology
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#20
Heloísa Lizotti Cilião, Rossana Batista Oliveira Camargo-Godoy, Marilesia Ferreira de Souza, Mariana Bisarro Dos Reis, Lorena Iastrenski, Vinicius Daher Alvares Delfino, Silvia Regina Rogatto, Ilce Mara de Syllos Cólus
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype-gene expression associations were also assessed...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
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