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https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#1
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...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28526484/regulation-of-cacybp-sip-expression-by-nfat1-transcription-factor
#2
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...
May 11, 2017: Immunobiology
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#3
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
https://www.readbyqxmd.com/read/28523202/identification-of-a-novel-alternatively-spliced-form-of-inflammatory-regulator-swap-70-like-adapter-of-t-cells
#4
Marie Hashimoto, Jun-Ichi Nagao, Shojiro Ikezaki, Sonoko Tasaki, Ken-Ichi Arita-Morioka, Yuka Narita, Tamaki Cho, Kenji Yuasa, Amnon Altman, Yoshihiko Tanaka
Activation of naive CD4(+) T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4(+) T cell inflammatory responses by controlling Ca(2+)/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2-7 of the Def6 gene...
2017: International Journal of Inflammation
https://www.readbyqxmd.com/read/28506889/nfam1-signaling-enhances-osteoclast-formation-and-bone-resorption-activity-in-paget-s-disease-of-bone
#5
Yuvaraj Sambandam, Kumaran Sundaram, Takamitsu Saigusa, Sundaravadivel Balasubramanian, Sakamuri V Reddy
Paget's disease of bone (PDB) is marked by the focal activity of abnormal osteoclasts (OCLs) with excess bone resorption. We previously detected measles virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB. Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the mechanism by which MVNP induces excess OCLs/bone resorption activity is unclear. Microarray analysis identified MVNP induction of NFAM1 (NFAT activating protein with ITAM motif 1) expression. Therefore, we hypothesize that MVNP induction of NFAM1 enhances OCL differentiation and bone resorption in PDB...
May 12, 2017: Bone
https://www.readbyqxmd.com/read/28505967/nfatc2-modulates-microglial-activation-in-the-a%C3%AE-pp-ps1-mouse-model-of-alzheimer-s-disease
#6
Gunjan D Manocha, Atreyi Ghatak, Kendra L Puig, Susan D Kraner, Christopher M Norris, Colin K Combs
Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28495529/mek-erk-and-calcineurin-nfat-mediated-mechanism-of-cerebral-hyperemia-and-brain-injury-following-nmda-receptor-activation
#7
Yuki Kurauchi, Rintaro Kinoshita, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Kunio Ishii
N-methyl-d-aspartate (NMDA) receptor activation increases regional cerebral blood flow (rCBF) and induces neuronal injury, but similarities between these processes are poorly understood. In this study, by measuring rCBF in vivo, we identified a clear correlation between cerebral hyperemia and brain injury. NMDA receptor activation induced brain injury as a result of rCBF increase, which was attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin. Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor of activated T-cell (NFAT) in neurons...
May 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28478803/peptide-11r-vivit-stimulates-osteoblastogenesis-through-regulating-the-expression-of-nuclear-factor-of-activated-t-cells-cytoplasmic-1
#8
M Li, X Wang, Z Bian, W Yao, Q He, F Tian, J Zhang, L Zhu
Osteoporosis is characterized by the imbalance of two relatively independent processes-osteoblastogenesis and osteoclastogenesis. Calcineurin (Cn)/nuclear factor of activated T cells (NFAT)(Cn/NFAT) signaling pathway is involved in these two processes in bone metabolism, but its potential as a target to treat osteoporosis needs to be defined. The aim of this study is to investigate the inhibition of polypeptide 11R-VIVIT onCn/NFAT signaling pathway. Rat calvaria (RC) cells were prepared from experimental model of osteoporosis in rat...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28477019/nfatc3-mediates-the-sensitivity-of-gastric-cancer-cells-to-arsenic-sulfide
#9
Xiuli Zhang, Ting Kang, Lian Zhang, Yingying Tong, Wenping Ding, Siyu Chen
Arsenic sulfide (As4S4) is the main component of Realgar which is widely used in traditional Chinese medicine. Previously we showed that As4S4 inhibited the proliferation of colon cancer cells through regulating nuclear factor of activated T cells (NFAT) pathway. Here we explore the role of NFAT in gastric cancer. We showed that As4S4 inhibited the expression of NFATc1, NFATc3, and NFATc4, and modulated the expression of NFATc2 accompanying with p53. The baseline expression of NFATc3 varied distinctly in gastric cancer cell lines (AGS, MGC803, MKN28, MKN45, and SGC7901) and the sensitivity of these cells to As4S4 was dissimilar, with AGS and MGC803 cells showing higher sensitivity while the SGC7901 cells relatively resistant...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28473706/molecular-mechanisms-underlying-the-evolution-of-the-slp76-signalosome
#10
Xuemei Qu, Xin Lan, Chong Deng, Jiatao Zhou, Jingjing Du, Shengfeng Huang, Yingqiu Li
The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h)...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464781/in-vitro-and-in-vivo-experimental-models-based-approaches-for-investigating-the-anti-inflammatory-profile-and-potential-of-coumarins
#11
Silvana Virginia Gagliotti Vigil de Mello, Tânia Silvia Fröde
BACKGROUND: Coumarins belong to the class of polyphenolic compounds and are often used as complementary and alternative medicines to treat inflammatory conditions. OBJECTIVE: In this study, we reviewed reports that involved in vivo and in vitro experimental model-based approaches investigating the potential anti-inflammatory properties of coumarins. METHODS: A literature search was performed using PUBMED, MEDLINE, Web of Science, and Scopus from 1 January 2005 to 31 December 2015...
May 2, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28447738/telmisartan-suppresses-cardiac-hypertrophy-by-inhibiting-cardiomyocyte-apoptosis-via-the-nfat-anp-bnp-signaling-pathway
#12
Xiurong Li, Yuhuai Lan, Yan Wang, Minghao Nie, Yanhong Lu, Eryang Zhao
Telmisartan, a type of angiotensin II (Ang II) receptor inhibitor, is a common agent used to treat hypertension in the clinic. Hypertension increases cardiac afterload and promotes cardiac hypertrophy. However, the ventricular Ang II receptor may be activated in the absence of hypertension. Therefore, telmisartan may reduce cardiac hypertrophy by indirectly ameliorating hypertensive symptoms and directly inhibiting the cardiac Ang II receptor. Nuclear factor of activated T‑cells (NFAT) contributes to cardiac hypertrophy via nuclear translocation, which induces a cascade of atrial natriuretic peptide (ANP) and brain/B‑type natriuretic peptide (BNP) expression and cardiomyocyte apoptosis...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446591/nfat5-sensitive-orai1-expression-and-store-operated-ca-2-entry-in-megakaryocytes
#13
Itishri Sahu, Lisann Pelzl, Basma Sukkar, Hajar Fakhri, Tamer Al-Maghout, Hang Cao, Stefan Hauser, Ravi Gutti, Meinrad Gawaz, Florian Lang
The transcription factor NFAT5 is up-regulated in several clinical disorders including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase (SGK)-1. The kinase is a powerful regulator of Orai1, a Ca(2+)-channel accomplishing store-operated Ca(2+)-entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca(2+) sensors stromal interaction molecule (STIM)-1, or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca(2+)-signaling in megakaryocytes...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28445076/image-based-phenotypic-screening-with-human-primary-t-cells-using-one-dimensional-imaging-cytometry-with-self-tuning-statistical-gating-algorithms
#14
Steve S Wang, Daniel J Ehrlich
The parallel microfluidic cytometer (PMC) is an imaging flow cytometer that operates on statistical analysis of low-pixel-count, one-dimensional (1D) line scans. It is highly efficient in data collection and operates on suspension cells. In this article, we present a supervised automated pipeline for the PMC that minimizes operator intervention by incorporating multivariate logistic regression for data scoring. We test the self-tuning statistical algorithms in a human primary T-cell activation assay in flow using nuclear factor of activated T cells (NFAT) translocation as a readout and readily achieve an average Z' of 0...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#15
J Triñanes, A E Rodriguez-Rodriguez, Y Brito, A Wagner, A P J De Vries, G Cuesto, A Acebes, E Salido, A Torres, E Porrini
β-cell transcription factors like: FoxO1, MafA, PDX-1, NeuroD, are dysfunctional in type 2 diabetes (T2DM). PTDM resembles T2DM and reflects interaction between pre-transplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors. We evaluated the effect of tacrolimus, cyclosporine-A and metabolic stressors (glucose+palmitate) on insulinoma β-cells (INS-1) in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for five days with 100μM palmitate and 22mM glucose; cyclosporin-A (250ng/mL) or tacrolimus (15ng/mL) were added the last 48h...
April 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28424684/modulation-of-human-leukocyte-antigen-c-by-human-cytomegalovirus-stimulates-kir2ds1-recognition-by-natural-killer-cells
#16
Kattria van der Ploeg, Chiwen Chang, Martin A Ivarsson, Ashley Moffett, Mark R Wills, John Trowsdale
The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424266/disease-associated-extracellular-loop-mutations-in-the-adhesion-g-protein-coupled-receptor-g1-adgrg1-gpr56-differentially-regulate-downstream-signaling
#17
Ayush Kishore, Randy A Hall
Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as GPR56) underlie the neurological disorder bilateral frontoparietal polymicrogyria (BFPP). Disease-associated mutations in G1 studied to date are believed to induce complete loss of receptor function, either through disruption of receptor trafficking or signaling activity. Given that N-terminal truncation of G1 and other adhesion G protein-coupled receptors has been shown to significantly increase the receptors' constitutive signaling, we examined two different BFPP-inducing extracellular loop mutations (R565W and L640R) in the context of both full-length and N-terminally truncated (deltaNT) G1...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28424240/the-histone-acetyltransferase-gcn5-positively-regulates-t-cell-activation
#18
Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang
Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28423341/glutathione-primes-t-cell-metabolism-for-inflammation
#19
Tak W Mak, Melanie Grusdat, Gordon S Duncan, Catherine Dostert, Yannic Nonnenmacher, Maureen Cox, Carole Binsfeld, Zhenyue Hao, Anne Brüstle, Momoe Itsumi, Christian Jäger, Ying Chen, Olaf Pinkenburg, Bärbel Camara, Markus Ollert, Carsten Bindslev-Jensen, Vasilis Vasiliou, Chiara Gorrini, Philipp A Lang, Michael Lohoff, Isaac S Harris, Karsten Hiller, Dirk Brenner
Activated T cells produce reactive oxygen species (ROS), which trigger the antioxidative glutathione (GSH) response necessary to buffer rising ROS and prevent cellular damage. We report that GSH is essential for T cell effector functions through its regulation of metabolic activity. Conditional gene targeting of the catalytic subunit of glutamate cysteine ligase (Gclc) blocked GSH production specifically in murine T cells. Gclc-deficient T cells initially underwent normal activation but could not meet their increased energy and biosynthetic requirements...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28419336/ip3r-mediated-ca2-signals-govern-hematopoietic-and-cardiac-divergence-of-flk1-cells-via-the-calcineurin-nfatc3-etv2-pathway
#20
Yi-Jie Wang, Jijun Huang, Wenqiang Liu, Xiaochen Kou, Huayuan Tang, Hong Wang, Xiujian Yu, Shaorong Gao, Kunfu Ouyang, Huang-Tian Yang
Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced Flk1+/PDGFRα- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes...
April 13, 2017: Journal of Molecular Cell Biology
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