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https://www.readbyqxmd.com/read/28214951/inhibition-of-jak-stat-pathway-restrains-tslp-activated-dendritic-cells-mediated-inflammatory-t-helper-type-2-cell-response-in-allergic-rhinitis
#1
Zhaohui Shi, Weihong Jiang, Min Wang, Xiaocheng Wang, Xiaoyuan Li, Xiaodong Chen, Li Qiao
Thymic stromal lymphopoietin (TSLP) has recently been implicated as a key molecule for initiating allergic rhinitis (AR) at the cell-dendritic cell (DC) interface. Previous studies demonstrated that TSLP activated DCs to express more OX40 ligand (OX40L), which is associated with the initiation of T helper type 2 (Th2) cell responses. STAT phosphorylation has been reported to be promoted by TSLP. Thus, we investigated if the JAK/STAT pathway inhibitor CYT387 could affect TSLP-DC-mediated Th2 cell response in naive T cell and AR mice model...
February 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#2
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214598/three-stats-are-involved-in-the-regulation-of-the-expression-of-antimicrobial-peptides-in-the-triangle-sail-mussel-hyriopsis-cumingii
#3
Yun-Jia Dai, Kai-Min Hui, Ying-Hao Zhang, Yan Liu, Yu-Qing Wang, Li-Juan Zhao, Li Lin, Lian-Qin Chai, Shun Wei, Jiang-Feng Lan
Janus kinase (Jak) and signal transducers and activators of transcription (STAT) signaling pathway is associated in antiviral and antibacterial immune response. Previous studies primarily investigated the function of STATs in mammals. For most invertebrates, only one STAT was found in each species, such as STAT92E was found in Drosophila melanogaster. The studies, which focus on the functional difference between various STATs in the same species of invertebrate, are limited. In the present study, three STATs (HcSTAT1, HcSTAT2 and HcSTAT3) were identified in triangle shell pearl mussel, Hyriopsis cumingii...
February 15, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28214593/jak-stat-pathway-directed-therapy-of-t-cell-leukemia-lymphoma-inspired-by-functional-and-structural-genomics
#4
REVIEW
Thomas A Waldmann
Abnormal activation of the γc cytokine JAK/STAT signaling pathway assessed by STAT3 or STAT5b phosphorylation was present in a proportion of many T-cell malignancies. Activating mutations of STAT3/STAT5b and JAK1/3 were present in some but not in all cases with constitutive signaling pathway activation. Using shRNA analysis pSTAT malignant T-cell lines were addicted to JAKs/STATs whether they were mutated or not. Activating JAK/STAT mutations were not sufficient to support leukemic cell proliferation but only augmented upstream pathway signals...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#5
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28210003/differential-signaling-through-p190-and-p210-bcr-abl-fusion-proteins-revealed-by-interactome-and-phosphoproteome-analysis
#6
J A Cutler, R Tahir, S K Sreenivasamurthy, C Mitchell, S Renuse, R S Nirujogi, A H Patil, M Heydarian, X Wong, X Wu, T-C Huang, M-S Kim, K Reddy, A Pandey
Two major types of leukemogenic BCR-ABL fusion proteins are p190(BCR-ABL) and p210(BCR-ABL). Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein-protein interaction analysis using biotinylation identification (BioID) with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28209720/acquired-expression-of-cbl-q367p-in-mice-induces-dysplastic-myelopoiesis-mimicking-chronic-myelomonocytic-leukemia
#7
Yuichiro Nakata, Takeshi Ueda, Akiko Nagamachi, Norimasa Yamasaki, Ken-Ichiro Ikeda, Yasuyuki Sera, Keiyo Takubo, Akinori Kanai, Hideaki Oda, Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji, Yasuhiro Ebihara, Linda Wolff, Zen-Ichiro Honda, Toshio Suda, Toshiya Inaba, Hiroaki Honda
Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by uncontrolled proliferation of dysplastic myelomonocytes and frequent progression to acute myeloid leukemia (AML). We identified mutations in the Cbl gene, which encodes a negative regulator of cytokine signaling, in a subset of CMML patients. To investigate the contribution of mutant Cbl in CMML pathogenesis, we generated conditional knock-in mice for Cbl that express wild-type Cbl in a steady state and inducibly express Cbl(Q367P) , a CMML-associated Cbl mutant...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28205646/connexin30-3-is-expressed-in-mouse-embryonic-stem-cells-and-is-responsive-to-leukemia-inhibitory-factor
#8
Mikako Saito, Yuma Asai, Keiichi Imai, Shoya Hiratoko, Kento Tanaka
The expression of 19 connexin (Cx) isoforms was observed in the mouse embryonic stem (ES) cell line, EB3. Their expression patterns could be classified into either pluripotent state-specific, differentiating stage-specific, or non-specific Cxs. We focused on Cx30.3 as typical of the first category. Cx30.3 was pluripotent state-specific and upregulated by leukemia inhibitory factor (LIF), a specific cytokine that maintains the pluripotent state of ES cell, via a Jak signaling pathway. Cx30.3 protein was localized to both the cell membrane and cytosol...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204819/lncrna-co-expression-network-model-for-the-prognostic-analysis-of-acute-myeloid-leukemia
#9
Jia-Qi Pan, Yan-Qing Zhang, Jing-Hua Wang, Ping Xu, Wei Wang
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with great variability of prognostic behaviors. Previous studies have reported that long non-coding RNAs (lncRNAs) play an important role in AML and may thus be used as potential prognostic biomarkers. However, thus use of lncRNAs as prognostic biomarkers in AML and their detailed mechanisms of action in this disease have not yet been well characterized. For this purpose, in the present study, the expression levels of lncRNAs and mRNAs were calculated using the RNA-seq V2 data for AML, following which a lncRNA‑lncRNA co-expression network (LLCN) was constructed...
February 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202754/jak-stat-signaling-pathways-and-inhibitors-affect-reversion-of-envelope-mutated-hiv-1
#10
Yudong Quan, Hongtao Xu, Yingshan Han, Thibault Mesplède, Mark A Wainberg
HIV can spread by both cell-free and cell-to-cell transmission. Here, we show that numerous of the amino acid changes in Env that are close to the CD4 binding pocket can affect HIV replication. We generated a number of mutant viruses that were unable to infect T cells as cell-free viruses but were nevertheless able to infect certain T cell lines as cell-associated viruses, followed by reversion to wild type. However, the activation of JAK-STAT signaling pathways caused inhibition of such cell-to-cell infection as well as the reversion of multiple HIV Env mutants that displayed differences in ability to bind to the CD4 receptor...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202313/the-complex-roles-of-stat3-and-stat5-in-maintaining-redox-balance-lessons-from-stat-mediated-xct-expression-in-cancer-cells
#11
Katja Linher-Melville, Gurmit Singh
STAT3 and STAT5 mediate diverse cellular processes, transcriptionally regulating gene expression and interacting with cytoplasmic proteins. Their canonical activity is stimulated by cytokines/growth factors through JAK-STAT signaling. As targets of oncogenes with intrinsic tyrosine kinase activity, STAT3 and STAT5 become constitutively active in hematologic neoplasms and solid tumors, promoting cell proliferation and survival and modulating redox homeostasis. This review summarizes reactive oxygen species (ROS)-regulated STAT activation and how STATs influence ROS production...
February 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28197101/the-combination-of-three-components-derived-from-sheng-maisan-protects-myocardial-ischemic-diseases-and-inhibits-oxidative-stress-via-modulating-mapks-and-jak2-stat3-signaling-pathways-based-on-bioinformatics-approach
#12
Fang Li, Yu Zhang, Donglin Zeng, Yu Xia, Xiaoxue Fan, Yisha Tan, Junping Kou, Boyang Yu
GRS is a drug combination of three components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula Sheng MaiSan, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study illuminates its underlying mechanisms against myocardial ischemic diseases based on the combined methods of bioinformatic prediction and experimental verification. A protein database was established through constructing the drug-protein network...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#13
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28196077/enhancer-of-polycomb-coordinates-multiple-signaling-pathways-to-promote-both-cyst-and-germline-stem-cell-differentiation-in-the-drosophila-adult-testis
#14
Lijuan Feng, Zhen Shi, Xin Chen
Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28195391/rig-i-is-a-key-antiviral-interferon-stimulated-gene-against-hepatitis-e-virus-dispensable-of-interferon-production
#15
Lei Xu, Wenshi Wang, Yunlong Li, Xinying Zhou, Yuebang Yin, Yijin Wang, Robert A de Man, Luc J W van der Laan, Fen Huang, Nassim Kamar, Maikel P Peppelenbosch, Qiuwei Pan
: Interferons (IFNs) are broad antiviral cytokines that exert their function by inducing the transcription of hundreds of interferon-stimulated genes (ISGs). However, little is known about the antiviral potential of these cellular effectors on hepatitis E virus (HEV) infection, the leading cause of acute hepatitis globally. In this study, we profiled the antiviral potential of a panel of important human ISGs on HEV replication in cell culture models by overexpression of individual ISG...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194647/cofilin-mediates-lps-induced-microglial-cell-activation-and-associated-neurotoxicity-through-activation-of-nf-%C3%AE%C2%BAb-and-jak-stat-pathway
#16
Qasim Alhadidi, Zahoor A Shah
Microglial cells are activated in response to different types of injuries or stress in the CNS. Such activation is necessary to get rid of the injurious agents and restore tissue homeostasis. However, excessive activation of microglial cells is harmful and contributes to secondary injury. Pertinently, microglial cell activity was targeted in many preclinical and clinical studies but such strategy failed in clinical trials. The main reason behind the failed attempts is the complexity of the injury mechanisms which needs either a combination therapy or targeting a process that is involved in multiple pathways...
February 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28194183/regulation-of-stem-cell-properties-of-m%C3%A3-ller-glia-by-jak-stat-and-mapk-signaling-in-the-mammalian-retina
#17
REVIEW
Krista M Beach, Jianbo Wang, Deborah C Otteson
In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28193636/evaluation-of-jak3-biology-in-autoimmune-disease-using-a-highly-selective-irreversible-jak3-inhibitor
#18
Fiona Elwood, David Witter, Jennifer Piesvaux, Brian Kraybill, Nathan Bays, Carla Alpert, Peter Goldenblatt, Yujie Qu, Irena Ivanovska, Hyun-Hee Lee, Chi-Sung Chiu, Hao Tang, Mark E Scott, Sujal Deshmukh, Mark Zielstorff, Alan Byford, Kalyan Chakravarty, Lauren Dorosh, Alexy Rivkin, Joel Klappenbach, Bo-Sheng Pan, Ilona Kariv, Christopher Dinsmore, Deborah Slipetz, Peter Dandliker
Reversible Janus kinase (JAK) inhibitors such as Tofacitinib(Changelian, et al., 2003;Flanagan, et al., 2010) and Decernotinib(Farmer, et al., 2015;Mahajan, et al., 2015) block cytokine signaling and are efficacious in treating autoimmune diseases (Kremer, et al., 2009;Fleischmann, et al., 2015;Fleischmann, et al., 2015;Krueger, et al., 2016;Sandborn, et al., 2012). However therapeutic doses are limited due to inhibition of other JAK/STAT pathways associated with hematopoiesis, lipid biogenesis, infection and immune responses(Kahn C, 2012)...
February 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28191885/molecular-definition-of-a-metastatic-lung-cancer-state-reveals-a-targetable-cd109-janus-kinase-stat-axis
#19
Chen-Hua Chuang, Peyton G Greenside, Zoë N Rogers, Jennifer J Brady, Dian Yang, Rosanna K Ma, Deborah R Caswell, Shin-Heng Chiou, Aidan F Winters, Barbara M Grüner, Gokul Ramaswami, Andrew L Spencley, Kimberly E Kopecky, Leanne C Sayles, E Alejandro Sweet-Cordero, Jin Billy Li, Anshul Kundaje, Monte M Winslow
Lung cancer is the leading cause of cancer deaths worldwide, with the majority of mortality resulting from metastatic spread. However, the molecular mechanism by which cancer cells acquire the ability to disseminate from primary tumors, seed distant organs, and grow into tissue-destructive metastases remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival...
February 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28188673/socs-potential-immune-checkpoint-molecules-for-cancer-immunotherapy
#20
REVIEW
Shunsuke Chikuma, Mitsuhiro Kanamori, Setsuko Mise-Omata, Akihiko Yoshimura
Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals, respectively. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine Interferon-γ (IFNγ) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway...
February 11, 2017: Cancer Science
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