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pi3k AND autoimmune

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https://www.readbyqxmd.com/read/29127843/ifn-%C3%AE-regulates-th17-differentiation-partly-through-the-inhibition-of-osteopontin-in-experimental-autoimmune-encephalomyelitis
#1
Qing Zhao, Wenjing Cheng, Yebin Xi, Zheyi Cao, Yunzhi Xu, Ting Wu, Chengzhen Li, Xiaoyin Niu, Guangjie Chen
Multiple sclerosis (MS) and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases. Increased activation of CD4+T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. IFN-β is widely used in the treatment of MS and is found to decrease IL-17 and OPN production in MS patients and EAE mice. However, a definitive molecular mechanism has not yet been fully elucidated. In this study, we investigated the immunomodulatory effect of IFN-β on the EAE model...
November 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29115519/pten-promotes-apoptosis-of-h2o2%C3%A2-injured-rat-nasal-epithelial-cells-through-pi3k-akt-and-other-pathways
#2
Minghui Jia, Xiaoyun Chen, Jili Liu, Jun Chen
Chronic rhinosinusitis (CRS) is a form of chronic inflammation of the nasal cavity and paranasal sinus with multi‑causal pathogenesis, including oxidative stress. Several lines of evidence have demonstrated that the phosphatase and tensin homolog gene (PTEN) can inhibit the activation of phosphoinositide 3‑kinase (PI3K) to affect phosphorylation of Akt. Importantly, the PI3K/PTEN/Akt signaling pathway is associated with various types of tumors, chronic inflammatory diseases, and autoimmune disease through its regulation of cell growth, apoptosis, proliferation, and metabolism...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109121/glycogen-synthase-kinase-3-modulates-cbl-b-and-constrains-t-cell-activation
#3
Charles W Tran, Samuel D Saibil, Thierry Le Bihan, Sara R Hamilton, Karl S Lang, Han You, Amy E Lin, Kristine M Garza, Alisha R Elford, Kelly Tai, Michael E Parsons, Kip Wigmore, Mitchell G Vainberg, Josef M Penninger, James R Woodgett, Tak W Mak, Pamela S Ohashi
The decision between T cell activation and tolerance is governed by the spatial and temporal integration of diverse molecular signals and events occurring downstream of TCR and costimulatory or coinhibitory receptor engagement. The PI3K-protein kinase B (PKB; also known as Akt) signaling pathway is a central axis in mediating proximal signaling events of TCR and CD28 engagement in T cells. Perturbation of the PI3K-PKB pathway, or the loss of negative regulators of T cell activation, such as the E3 ubiquitin ligase Cbl-b, have been reported to lead to increased susceptibility to autoimmunity...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29099860/autoimmunity-and-autoinflammation-a-systems-view-on-signaling-pathway-dysregulation-profiles
#4
Arsen Arakelyan, Lilit Nersisyan, David Poghosyan, Lusine Khondkaryan, Anna Hakobyan, Henry Löffler-Wirth, Evie Melanitou, Hans Binder
INTRODUCTION: Autoinflammatory and autoimmune disorders are characterized by aberrant changes in innate and adaptive immunity that may lead from an initial inflammatory state to an organ specific damage. These disorders possess heterogeneity in terms of affected organs and clinical phenotypes. However, despite the differences in etiology and phenotypic variations, they share genetic associations, treatment responses and clinical manifestations. The mechanisms involved in their initiation and development remain poorly understood, however the existence of some clear similarities between autoimmune and autoinflammatory disorders indicates variable degrees of interaction between immune-related mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28964592/interleukin-7-receptor-alpha-thr244ile-genetic-polymorphism-is-associated-with-susceptibility-and-prognostic-markers-in-breast-cancer-subgroups
#5
Glauco Akelinghton Freire Vitiello, Roberta Losi Guembarovski, Marla Karine Amarante, Jesus Roberto Ceribelli, Elaine Cristina Baraldi Carmelo, Maria Angelica Ehara Watanabe
Interleukin-7 (IL-7) exerts crucial functions on lymphoid cells' development and maintenance. In breast cancer (BC), IL-7 promotes growth of tumor cells in culture through the activation of JAK1/3-STAT5 and PI3K/AKT pathways, and expression of IL-7 signaling components was associated with worst prognosis. AC>T polymorphism (rs6897932; Thr244Ile) at exon 6 of IL-7 receptor alpha (IL-7Rα) gene (IL7RA) shifts the balance between the membrane-bound and soluble IL-7Rα splicing variants and was previously associated with autoimmune diseases, but has not been studied in cancer, including BC, so far...
September 28, 2017: Cytokine
https://www.readbyqxmd.com/read/28945111/pi3k%C3%AE-selective-and-pi3k%C3%AE-%C3%AE-combinatorial-inhibitors-in-clinical-development-for-b-cell-non-hodgkin-lymphoma
#6
REVIEW
Benjamin L Lampson, Jennifer R Brown
The efficacy of the prototypical phosphatidylinositol-3-kinase (PI3K) inhibitor idelalisib for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) has led to development of multiple compounds targeting this pathway. Areas Covered: We review the hypothesized therapeutic mechanisms of PI3K inhibitors, including abrogation of B cell receptor signaling, blockade of microenvironmental pro-survival signals, and enhancement of anti-tumor immunity. We examine toxicities of idelalisib, including bacterial infections (possibly secondary to drug-induced neutropenia), opportunistic infections (possibly attributable to on-target inhibition of T cell function), and organ toxicities such as transaminitis and enterocolitis (possibly autoimmune, secondary to on-target inhibition of p110δ in regulatory T cells)...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28855209/therapeutic-targeting-of-oncogenic-tyrosine-phosphatases
#7
REVIEW
Rochelle Frankson, Zhi-Hong Yu, Yunpeng Bai, Qinglin Li, Ruo-Yu Zhang, Zhong-Yin Zhang
Protein tyrosine phosphatases (PTP) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTK) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor-mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades that regulate cell functions...
August 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28833093/multifaceted-role-of-il-21-in-rheumatoid-arthritis-current-understanding-and-future-perspectives
#8
REVIEW
Palani Dinesh, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder designated with hyperplastic synovium, bone destruction and cartilage degradation. Current therapies involve targeting major cytokines and inflammatory mediators involved in RA to alleviate the pain and provide a temporary relief. Interleukin 21 (IL-21), a recently identified cytokine is known to possess a versatile role in modulating the cells of the RA synovium. Over the past decade, the pleiotropic role of IL-21 in RA pathogenesis has been implicated in several aspects...
August 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28736524/immune-and-metabolic-regulation-mechanism-of-dangguiliuhuang-decoction-against-insulin-resistance-and-hepatic-steatosis
#9
Hui Cao, Lingling Tuo, Yali Tuo, Ziyun Xia, Rong Fu, Yang Liu, Yihong Quan, Jue Liu, Zhihong Yu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28733141/gastrin-releasing-peptide-and-its-receptor-increase-arthritis-fibroblast-like-synoviocytes-invasiveness-through-activating-the-pi3k-akt-pathway
#10
Vanessa Schuck Clarimundo, Mirian Farinon, Renata Ternus Pedó, Vivian Oliveira Nunes Teixeira, Carolina Nör, Percio S Gulko, Ricardo Machado Xavier, Patricia Gnieslaw de Oliveira
Rheumatoid arthritis (RA) is an autoimmune disease that leads to joint destruction. The fibroblast-like synoviocytes (FLS) has a central role on the disease pathophysiology. The present study aimed to examine the role of gastrin-releasing peptide (GRP) and its receptor (GRPR) on invasive behavior of mice fibroblast-like synoviocytes (FLS), as well as to evaluate GRP-induced signaling on PI3K/AKT pathway. The expression of GRPR in FLS was investigated by immunocytochemistry, western blot (WB) and qRT-PCR. The proliferation and invasion were assessed by SRB and matrigel-transwell assay after treatment with GRP and/or RC-3095 (GRPR antagonist), and/or Ly294002 (inhibitor of PI3K/AKT pathway)...
July 18, 2017: Peptides
https://www.readbyqxmd.com/read/28713374/the-selective-phosphoinoside-3-kinase-p110%C3%AE-inhibitor-ipi-3063-potently-suppresses-b-cell-survival-proliferation-and-differentiation
#11
Honyin Chiu, Sharmila Mallya, Phuongthao Nguyen, Annie Mai, Leandra V Jackson, David G Winkler, Jonathan P DiNitto, Erin E Brophy, Karen McGovern, Jeffery L Kutok, David A Fruman
The class I phosphoinoside-3-kinases (PI3Ks) are important enzymes that relay signals from cell surface receptors to downstream mediators driving cellular functions. Elevated PI3K signaling is found in B cell malignancies and lymphocytes of patients with autoimmune disease. The p110δ catalytic isoform of PI3K is a rational target since it is critical for B lymphocyte development, survival, activation, and differentiation. In addition, activating mutations in PIK3CD encoding p110δ cause a human immunodeficiency known as activated PI3K delta syndrome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28696014/effect-of-metformin-on-ossification-and-inflammation-of-fibroblasts-in-ankylosing-spondylitis-an-in-vitro-study
#12
Xiong Qin, Tongmeng Jiang, Sijia Liu, Jiachang Tan, Huayu Wu, Li Zheng, Jinmin Zhao
Ankylosing spondylitis (AS) is an autoimmune disease characterized by fibroblasts ossification. However, effective drug therapy for AS is lacking. As an antidiabetic drug, metformin has demonstrated an antiosteogenic effect on osteoblasts in vitro. And it is also a kind of specific agonists for adenosine 5'-monophosphate activated protein kinase (AMPK), which is blocked in the process of AS. Given the role in antiosteogenesis and AMPK activating, metformin was investigated of its effect on fibroblasts harvested from capsular ligament of patients with femoral neck fracture and AS...
July 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28676205/small-molecules-to-the-rescue-inhibition-of-cytokine-signaling-in-immune-mediated-diseases
#13
REVIEW
Massimo Gadina, Nathalia Gazaniga, Laura Vian, Yasuko Furumoto
Cytokines are small, secreted proteins associated with the maintenance of immune homeostasis but also implicated with the pathogenesis of several autoimmune and inflammatory diseases. Biologic agents blocking cytokines or their receptors have revolutionized the treatment of such pathologies. Nonetheless, some patients fail to respond to these drugs or do not achieve complete remission. The signal transduction originating from membrane-bound cytokine receptors is an intricate network of events that lead to gene expression and ultimately regulate cellular functionality...
July 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28581446/tregs-restrain-dendritic-cell-autophagy-to-ameliorate-autoimmunity
#14
Themis Alissafi, Aggelos Banos, Louis Boon, Tim Sparwasser, Alessandra Ghigo, Kajsa Wing, Dimitrios Vassilopoulos, Dimitrios Boumpas, Triantafyllos Chavakis, Ken Cadwell, Panayotis Verginis
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28499934/matrine-promotes-oligodendrocyte-development-in-cns-autoimmunity-through-the-pi3k-akt-signaling-pathway
#15
Shu-Qing Liu, Ming-Liang Zhang, HUi-Jun Zhang, Fang-Zhou Liu, Rao-Juan Chu, Guang-Xian Zhang, Lin Zhu
AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset...
July 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28485793/lipoxin-a4-mitigates-experimental-autoimmune-myocarditis-by-regulating-inflammatory-response-nf-%C3%AE%C2%BAb-and-pi3k-akt-signaling-pathway-in-mice
#16
Y Shi, H Pan, H-Z Zhang, X-Y Zhao, J Jin, H-Y Wang
OBJECTIVE: Myocarditis, an acute inflammation disease of the heart, is a potentially lethal disease and can lead to sudden death. This study aims to investigate the therapeutic effect of lipoxin A4 (LXA4) on experimental autoimmune myocarditis (EAM) and to explore the underlying mechanism. MATERIALS AND METHODS: EAM was induced in BALB/c mice by injection of porcine cardiac myosin and LAX4 at doses of 10 or 50 μg/kg was administrated from day 1 to 21. The severity of myocarditis was evaluated by detection of heart weight/body weight (HW/BW) ratio and histopathological examination of the heart...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28480512/regulation-of-immune-cell-signaling-by-ship1-a-phosphatase-scaffold-protein-and-potential-therapeutic-target
#17
REVIEW
Samantha D Pauls, Aaron J Marshall
The phosphoinositide phosphatase SHIP is a critical regulator of immune cell activation. Despite considerable study, the mechanisms controlling SHIP activity to ensure balanced cell activation remain incompletely understood. SHIP dampens BCR signaling in part through its association with the inhibitory coreceptor Fc gamma receptor IIB, and serves as an effector for other inhibitory receptors in various immune cell types. The established paradigm emphasizes SHIP's inhibitory receptor-dependent function in regulating phosphoinositide 3-kinase signaling by dephosphorylating the phosphoinositide PI(3,4,5)P3 ; however, substantial evidence indicates that SHIP can be activated independently of inhibitory receptors and can function as an intrinsic brake on activation signaling...
June 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28468969/protein-kinase-ck2-controls-the-fate-between-th17-cell-and-regulatory-t-cell-differentiation
#18
Sara A Gibson, Wei Yang, Zhaoqi Yan, Yudong Liu, Amber L Rowse, Amy S Weinmann, Hongwei Qin, Etty N Benveniste
CK2 is a highly conserved and pleiotropic serine/threonine kinase that promotes many prosurvival and proinflammatory signaling pathways, including PI3K/Akt/mTOR and JAK/STAT. These pathways are essential for CD4(+) T cell activation and polarization, but little is known about how CK2 functions in T cells. In this article, we demonstrate that CK2 expression and kinase activity are induced upon CD4(+) T cell activation. Targeting the catalytic activity of CK2 using the next-generation small molecule inhibitor CX-4945 in vitro significantly and specifically inhibited mouse and human Th17 cell differentiation while promoting the generation of Foxp3(+) regulatory T cells (Tregs)...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28462209/lung-ischemia-reperfusion-injury-the-therapeutic-role-of-dipeptidyl-peptidase-4-inhibition
#19
REVIEW
Paul A J Beckers, Jan F Gielis, Paul E Van Schil, Dirk Adriaensen
Dipeptidyl peptidase 4 (DPP4) is a cell surface protease that has been reported to play a role in glucose homeostasis, cancer, HIV, autoimmunity, immunology and inflammation. A role for DPP4 in ischemia-reperfusion injury (IRI) in the heart has been established. Dipeptidyl peptidase 4 inhibition (DPP4i) appeared to decrease infarct size, improves cardiac function and promotes myocardial regeneration. Lung ischemia reperfusion injury is caused by a complex mechanism in which macrophages and neutrophils play an important role...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28443090/immunometabolic-regulations-mediated-by-coinhibitory-receptors-and-their-impact-on-t-cell-immune-responses
#20
REVIEW
Nikolaos Patsoukis, Jessica D Weaver, Laura Strauss, Christoph Herbel, Pankaj Seth, Vassiliki A Boussiotis
Host immunity provides wide spectrum protection that serves to eradicate pathogens and cancer cells, while maintaining self-tolerance and immunological homeostasis. Ligation of the T cell receptor (TCR) by antigen activates signaling pathways that coordinately induce aerobic glycolysis, mitochondrial activity, anabolic metabolism, and T effector cell differentiation. Activation of PI3K, Akt, and mTOR triggers the switch to anabolic metabolism by inducing transcription factors such as Myc and HIF1, and the glucose transporter Glut1, which is pivotal for the increase of glucose uptake after T cell activation...
2017: Frontiers in Immunology
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