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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/28214598/three-stats-are-involved-in-the-regulation-of-the-expression-of-antimicrobial-peptides-in-the-triangle-sail-mussel-hyriopsis-cumingii
#2
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/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#3
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28212655/elderly-onset-hereditary-pulmonary-alveolar-proteinosis-and-its-cytokine-profile
#4
Masayuki Ito, Kazuyuki Nakagome, Hiromitsu Ohta, Keiichi Akasaka, Yoshitaka Uchida, Atsushi Hashimoto, Ayako Shiono, Toshinori Takada, Makoto Nagata, Jun Tohyama, Koichi Hagiwara, Minoru Kanazawa, Koh Nakata, Ryushi Tazawa
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. CASE PRESENTATION: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage...
February 17, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28204819/lncrna-co-expression-network-model-for-the-prognostic-analysis-of-acute-myeloid-leukemia
#5
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...
March 2017: International Journal of Molecular Medicine
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
#6
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/28202165/ghetting-to-know-adpkd-proliferative-signaling-stat
#7
Ching-Hsien Chen, Robert H Weiss
Due to their common pathogenesis and parallel proliferative signaling pathways, the cystic diseases have been recently studied in the context of cancer biology. The present study continues this paradigm by identifying signal transducer and activator of transcription (STAT5) and growth hormone (GH) as potentially modifiable pathways in polycystic kidney disease. GH, which is a potent activator of STAT5, has the additional possibility of being a biomarker, as well as providing a potential mechanism of action of somatostatin analogs in clinical trials...
March 2017: Kidney International
https://www.readbyqxmd.com/read/28192400/oncogenic-signaling-by-kit-tyrosine-kinase-occurs-selectively-on-the-golgi-apparatus-in-gastrointestinal-stromal-tumors
#8
Y Obata, K Horikawa, T Takahashi, Y Akieda, M Tsujimoto, J A Fletcher, H Esumi, T Nishida, R Abe
Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM)...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28176332/low-dose-interleukin-2-promotes-stat5-phosphorylation-treg-survival-and-ctla-4-dependent-function-in-autoimmune-liver-diseases
#9
Hannah C Jeffery, Louisa E Jeffery, Philipp Lutz, Margaret Corrigan, Gwilym J Webb, Gideon M Hirschfield, David H Adams, Ye Htun Oo
CD4(+) CD25(high) CD127(low) FOXP3(+) regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and regulatory T cells contribute to the pathogenesis of autoimmune diseases. We recently reported that the hepatic microenvironment is deficient in IL-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate STAT5 phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases...
February 8, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28167605/thymus-derived-treg-cell-development-is-regulated-by-c-type-lectin-mediated-bic-mirna155-expression
#10
Raquel Sánchez-Díaz, Rafael Blanco-Dominguez, Sandra Lasarte, Katerina Tsilingiri, Enrique Martín-Gayo, Beatriz Linillos-Pradillo, Hortensia de la Fuente, Francisco Sánchez-Madrid, Rinako Nakagawa, María L Toribio, Pilar Martín
Thymus-derived regulatory T cells (tTregs) are key to prevent autoimmune diseases but the mechanisms involved in their development remain unsolved. Here, we show that the C-type lectin receptor CD69 controls tTreg cell development and peripheral Treg homeostasis through the regulation of BIC/miR-155 and its target, the suppressor of cytokine signaling 1 (SOCS-1). Using Foxp3-mRFP/cd69(+/-) or/cd69(-/-) reporter mice, shRNA-mediated silencing and miR-155 transfection approaches, we found that CD69 deficiency impaired the signal transducer and activator of transcription 5 (STAT5) pathway in Foxp3(+) cells...
February 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28163905/stat5-and-cd4-t-cell-immunity
#11
REVIEW
David L Owen, Michael A Farrar
STAT5 plays a critical role in the development and function of many cell types. Here, we review the role of STAT5 in the development of T lymphocytes in the thymus and its subsequent role in the differentiation of distinct CD4 (+) helper and regulatory T-cell subsets.
2017: F1000Research
https://www.readbyqxmd.com/read/28154180/berberine-induced-inactivation-of-signal-transducer-and-activator-of-transcription-5-signaling-promotes-male-specific-expression-of-a-bile-acid-uptake-transporter
#12
Pengli Bu, Yuan Le, Yue Zhang, Youcai Zhang, Xingguo Cheng
Sodium-taurocholate co-transporting polypeptide (Ntcp/NTCP) is the major uptake transporter of bile salts in mouse and human livers. In certain diseases, including endotoxemia, cholestasis, diabetes, and hepatocarcinoma, Ntcp/NTCP expression is markedly reduced, which interferes with enterohepatic circulation of bile salts, impairing the absorption of lipophilic compounds. Therefore, normal Ntcp/NTCP expression in the liver is physiologically important. Berberine is an herbal medicine used historically to improve liver function and has recently been shown to repress signal transducer and activator of transcription (Stat) signaling...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28151427/pd-1-modulates-regulatory-t-cell-homeostasis-during-low-dose-il-2-therapy
#13
Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T Kim, Edwin P Alyea, Philippe Armand, Corey S Cutler, Vincent T Ho, Joseph H Antin, Robert J Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-Ichi Matsuoka
CD4+Foxp3+ regulatory T cells (Tregs) play a central role in the maintainance of immune tolerance after HSCT. We previously reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD, however, the mechanisms which regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with chronic GVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Treg and simultaneously enhanced the expression of Programmed death-1 (PD-1), especially on CD44(+)CD62L(+) central-memory Treg, while expression of other inhibitory molecules including CTLA-4, LAG-3 and TIM-3 remained stable...
February 1, 2017: Blood
https://www.readbyqxmd.com/read/28148688/extl3-mutations-cause-skeletal-dysplasia-immune-deficiency-and-developmental-delay
#14
Stefano Volpi, Yasuhiro Yamazaki, Patrick M Brauer, Ellen van Rooijen, Atsuko Hayashida, Anne Slavotinek, Hye Sun Kuehn, Maja Di Rocco, Carlo Rivolta, Ileana Bortolomai, Likun Du, Kerstin Felgentreff, Lisa Ott de Bruin, Kazutaka Hayashida, George Freedman, Genni Enza Marcovecchio, Kelly Capuder, Prisni Rath, Nicole Luche, Elliott J Hagedorn, Antonella Buoncompagni, Beryl Royer-Bertrand, Silvia Giliani, Pietro Luigi Poliani, Luisa Imberti, Kerry Dobbs, Fabienne E Poulain, Alberto Martini, John Manis, Robert J Linhardt, Marita Bosticardo, Sergio Damian Rosenzweig, Hane Lee, Jennifer M Puck, Juan Carlos Zúñiga-Pflücker, Leonard Zon, Pyong Woo Park, Andrea Superti-Furga, Luigi D Notarangelo
We studied three patients with severe skeletal dysplasia, T cell immunodeficiency, and developmental delay. Whole-exome sequencing revealed homozygous missense mutations affecting exostosin-like 3 (EXTL3), a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. Patient-derived fibroblasts showed abnormal HS composition and altered fibroblast growth factor 2 signaling, which was rescued by overexpression of wild-type EXTL3 cDNA. Interleukin-2-mediated STAT5 phosphorylation in patients' lymphocytes was markedly reduced...
February 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28147284/benzotriazoles-reactivate-latent-hiv-1-through-inactivation-of-stat5-sumoylation
#15
Alberto Bosque, Kyle A Nilson, Amanda B Macedo, Adam M Spivak, Nancie M Archin, Ryan M Van Wagoner, Laura J Martins, Camille L Novis, Matthew A Szaniawski, Chris M Ireland, David M Margolis, David H Price, Vicente Planelles
The presence of latent HIV-1 in infected individuals represents a major barrier preventing viral eradication. For that reason, reactivation of latent viruses in the presence of antiretroviral regimens has been proposed as a therapeutic strategy to achieve remission. We screened for small molecules and identified several benzotriazole derivatives with the ability to reactivate latent HIV-1. In the presence of IL-2, benzotriazoles reactivated and reduced the latent reservoir in primary cells, and, remarkably, viral reactivation was achieved without inducing cell proliferation, T cell activation, or cytokine release...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28131718/spleen-tyrosine-kinase-mediates-the-actions-of-epo-and-gm-csf-and-coordinates-with-tgf-%C3%AE-in-erythropoiesis
#16
Hua-Ching Chang, Duen-Yi Huang, Mai-Szu Wu, Ching-Liang Chu, Shiang-Jong Tzeng, Wan-Wan Lin
Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biological actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis...
January 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28130496/induction-of-il21-in-peripheral-t-follicular-helper-cells-is-an-indicator-of-influenza-vaccine-response-in-a-previously-vaccinated-hiv-infected-pediatric-cohort
#17
Lesley R de Armas, Nicola Cotugno, Suresh Pallikkuth, Li Pan, Stefano Rinaldi, M Celeste Sanchez, Louis Gonzalez, Alberto Cagigi, Paolo Rossi, Paolo Palma, Savita Pahwa
HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012-2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders...
January 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28125559/o-011-low-dose-il-2-administration-expands-human-regulatory-t-cells-in-patients-with-uc-and-humanized-mice-and-protects-against-experimental-colitis
#18
Jeremy Goettel, Daniel Kotlarz, David Illig, James Canavan, Jessica Allegretti, Matthew Hamilton, Ryan Kelly, Alexandra Griffith, Madeline Carellas, Anastasia Nelina, Athos Bousvaros, Joshua Korzenik, Scott Snapper
BACKGROUND: Treg dysfunction or deficiency results in unopposed immune activation and autoimmunity. Interleukin-2 (IL-2) is critical for the expansion, suppressive function, and maintenance of Tregs. Although conventional T cells and NK cells respond to IL-2, Tregs are more sensitive to lower concentrations of IL-2 due to constitutive expression of CD25, the high affinity IL-2 receptor. Low-dose IL-2 therapies have shown to preferentially expand Tregs and ameliorate manifestations of graft versus host disease (Koreth et al...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28117214/a-novel-jak-inhibitor-peficitinib-demonstrates-potent-efficacy-in-a-rat-adjuvant-induced-arthritis-model
#19
Misato Ito, Shunji Yamazaki, Kaoru Yamagami, Masako Kuno, Yoshiaki Morita, Kenji Okuma, Koji Nakamura, Noboru Chida, Masamichi Inami, Takayuki Inoue, Shohei Shirakami, Yasuyuki Higashi
The Janus kinase (JAK) family of tyrosine kinases is associated with various cytokine receptors. JAK1 and JAK3 play particularly important roles in the immune response, and their inhibition is expected to provide targeted immune modulation. Several oral JAK inhibitors have recently been developed for treating autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the pharmacological effects of peficitinib (formerly known as ASP015K), a novel, chemically synthesized JAK inhibitor. We found that peficitinib inhibited JAK1 and JAK3 with 50% inhibitory concentrations of 3...
December 23, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28115365/activation-of-ppar%C3%AE-by-endogenous-prostaglandin-j2-mediates-the-antileukemic-effect-of-selenium-in-murine-leukemia
#20
Emily R Finch, Diwakar B Tukaramrao, Laura L Goodfield, Michael D Quickel, Robert F Paulson, K Sandeep Prabhu
Supplementation with non-toxic doses of micronutrient selenium has been shown to alleviate chronic myelogenous leukemia (CML) via the elimination of leukemia stem cells (LSCs) in mice. This provides a new and novel method to eliminate the LSCs that are otherwise not targeted by existing therapies. The antileukemic effect of selenium was dependent on the production of endogenous cyclopentenone prostaglandins (CyPGs), delta-12 prostaglandin J2 (Δ(12)-PGJ2) and 15-deoxy-delta (12,14)- prostaglandin J2 (15d-PGJ2)...
January 23, 2017: Blood
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