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Hyo-Jin Kim, Hwa-Rim Lee, Ji-Young Seo, Hye Guk Ryu, Kyung-Ha Lee, Do-Yeon Kim, Kyong-Tai Kim
Nuclear factor, interleukin 3, regulated (Nfil3, also known as E4 Promoter-Binding Protein 4 (E4BP4)) protein is a transcription factor that binds to DNA and generally represses target gene expression. In the circadian clock system, Nfil3 binds to a D-box element residing in the promoter of clock genes and contributes to their robust oscillation. Here, we show that the 5'-untranslated region (5'-UTR) of Nfil3 mRNA contains an internal ribosome entry site (IRES) and that IRES-mediated translation occurs in a phase-dependent manner...
February 21, 2017: Scientific Reports
Graham J Britton, Ruth E Mitchell, Bronwen R Burton, David C Wraith
Secretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10+ T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration...
2017: PloS One
Wen-Xing Li, Kan He, Ling Tang, Shao-Xing Dai, Gong-Hua Li, Wen-Wen Lv, Yi-Cheng Guo, San-Qi An, Guo-Ying Wu, Dahai Liu, Jing-Fei Huang
Breast cancer is the most commonly diagnosed malignancy in women. Several key genes and pathways have been proven to correlate with breast cancer pathology. This study sought to explore the differences in key transcription factors (TFs), transcriptional regulation networks and dysregulated pathways in different tissues in breast cancer. We employed 14 breast cancer datasets from NCBI-GEO and performed an integrated analysis in three different tissues including breast, blood and saliva. The results showed that there were eight genes (CEBPD, EGR1, EGR2, EGR3, FOS, FOSB, ID1 and NFIL3) down-regulated in breast tissue but up-regulated in blood tissue...
January 24, 2017: Oncotarget
Jiaqi Chen, Ling Yu, Siwei Zhang, Xia Chen
Acute myocardial infarction (AMI) is a severe cardiovascular disease that is a serious threat to human life. However, the specific diagnostic biomarkers have not been fully clarified and candidate regulatory targets for AMI have not been identified. In order to explore the potential diagnostic biomarkers and possible regulatory targets of AMI, we used a network analysis-based approach to analyze microarray expression profiling of peripheral blood in patients with AMI. The significant differentially-expressed genes (DEGs) were screened by Limma and constructed a gene function regulatory network (GO-Tree) to obtain the inherent affiliation of significant function terms...
2016: Frontiers in Physiology
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
Cyril Seillet, Lisa A Mielke, Daniela B Amann-Zalcenstein, Shian Su, Jerry Gao, Francisca F Almeida, Wei Shi, Matthew E Ritchie, Shalin H Naik, Nicholas D Huntington, Sebastian Carotta, Gabrielle T Belz
Innate lymphoid cells (ILCs) are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF(+) ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical...
October 4, 2016: Cell Reports
Sujuan Wu, Junyi Li, Mushui Cao, Jing Yang, Yi-Xue Li, Yuan-Yuan Li
BACKGROUND: Glioma is the most common brain tumor and it has very high mortality rate due to its infiltration and heterogeneity. Precise classification of glioma subtype is essential for proper therapeutic treatment and better clinical prognosis. However, the molecular mechanism of glioma is far from clear and the classical classification methods based on traditional morphologic and histopathologic knowledge are subjective and inconsistent. Recently, classification methods based on molecular characteristics are developed with rapid progress of high throughput technology...
2016: BMC Systems Biology
Timothy K Erick, Courtney K Anderson, Emma C Reilly, Jack R Wands, Laurent Brossay
The submandibular salivary gland (SMG), a major site of persistent infection for many viruses, contains a large NK cell population. Using NFIL3-deficient mice, PLZF reporter/fate mapping mice, and mixed bone marrow chimeras, we identified two distinct populations of NK cells in the SMG. Although phenotypically unique, the main population relies on NFIL3, but not PLZF, for development and, therefore, is developmentally similar to the conventional NK cell subset. In contrast, we found that approximately one quarter of the SMG NK cells develop independently of NFIL3...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Timothy E O'Sullivan, Moritz Rapp, Xiying Fan, Orr-El Weizman, Priya Bhardwaj, Nicholas M Adams, Thierry Walzer, Andrew J Dannenberg, Joseph C Sun
Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency...
August 16, 2016: Immunity
M Jargosch, S Kröger, E Gralinska, U Klotz, Z Fang, W Chen, U Leser, J Selbig, D Groth, R Baumgrass
Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation...
June 24, 2016: Genetics and Molecular Research: GMR
Wenyu Wang, Yang Liu, Jingcan Hao, Shuyu Zheng, Yan Wen, Xiao Xiao, Awen He, Qianrui Fan, Feng Zhang, Ruiyu Liu
Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8)...
October 10, 2016: Gene
Mackenzie L Redhead, Nathália A Portilho, Allison M Felker, Shuhiba Mohammad, Danielle L Mara, B Anne Croy
Mice ablated for the gene encoding the transcription factor Nfil3 lack peripheral natural killer (NK) cells but retain tissue-resident NK cells, particularly in mucosal sites, including virgin uterus. We undertook a time course histological study of implantation sites from syngeneically (Nfil3(-/-)) and allogeneically (BALB/c) mated Nfil3(-/-) females. We also examined implantation sites from Rag2(-/-)Il2rg(-/-) females preconditioned by adoptive transfer of Nfil3(-/-) marrow or uterine cell suspensions to identify the Nfil3(-/-) pregnancy aberrations that could be attributed to nonlymphoid cells...
May 2016: Biology of Reproduction
Selma Boulenouar, Jean-Marc Doisne, Amanda Sferruzzi-Perri, Louise M Gaynor, Jens Kieckbusch, Elisa Balmas, Hong Wa Yung, Shagayegh Javadzadeh, Léa Volmer, Delia A Hawkes, Keli Phillips, Hugh J M Brady, Abigail L Fowden, Graham J Burton, Ashley Moffett, Francesco Colucci
Uterine NK cells are innate lymphoid cells (ILC) that populate the uterus and expand during pregnancy, regulating placental development and fetal growth in humans and mice. We have recently characterized the composition of uterine ILCs (uILCs), some of which require the transcription factor NFIL3, but the extent to which NFIL3-dependent cells support successful reproduction in mice is unknown. By mating Nfil3 (-/-) females with wild-type males, here we show the effects of NFIL3 deficiency in maternal cells on both the changes in uILCs during pregnancy and the downstream consequences on reproduction...
2016: Frontiers in Immunology
Yanbin Zhao, Karl Fent
Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated...
February 22, 2016: Scientific Reports
Konrad Pazdrak, Young Moon, Christof Straub, Susan Stafford, Alexander Kurosky
The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired pro-apoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex)...
April 2016: Apoptosis: An International Journal on Programmed Cell Death
Huan Li, Wen-Kai Li, Yuan-Fu Lu, Li-Xin Wei, Jie Liu
Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and "detoxification," and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods...
2016: PeerJ
Saïda Dadi, Sagar Chhangawala, Benjamin M Whitlock, Ruth A Franklin, Chong T Luo, Soyoung A Oh, Ahmed Toure, Yuri Pritykin, Morgan Huse, Christina S Leslie, Ming O Li
Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αβ, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1...
January 28, 2016: Cell
Juan Gambini, Lucía Gimeno-Mallench, Marta Inglés, Gloria Olaso, Kheira Mohamed Abdelaziz, Juan Antonio Avellana, Ángel Belenguer, Raquel Cruz, Cristina Mas-Bargues, Consuelo Borras, José Viña
INTRODUCTION: Longevity is determined by genetic and external factors, such as nutritional, environmental, social, etc. Nevertheless, when living conditions are optimal, longevity is determined by genetic variations between individuals. In a same population, with relative genotypic homogeneity, subtle changes in the DNA sequence affecting a single nucleotide can be observed. These changes, called single nucleotide polymorphisms (SNP) are present in 1-5% of the population. MATERIAL AND METHODS: A total of 92 subjects were recruited, including 28 centenarians and 64 controls, in order to find SNP that maybe implicated in the extreme longevity, as in the centenarians...
May 2016: Revista Española de Geriatría y Gerontología
Francisco Victorino, Dorothy K Sojka, Kelley S Brodsky, Eoin N McNamee, Joanne C Masterson, Dirk Homann, Wayne M Yokoyama, Holger K Eltzschig, Eric T Clambey
NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, infection, and/or transformation. Whereas conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. In the present study, we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying ischemic injury in the mouse kidney. Parabiosis experiments demonstrate that the kidney contains a significant fraction of trNK cells under homeostatic conditions...
November 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Haji Akbar, Fernanda Batistel, James K Drackley, Juan J Loor
In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration...
2015: PloS One
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