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pi3k AND autoimmune

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https://www.readbyqxmd.com/read/28199731/proteomic-profiling-analysis-reveals-a-link-between-experimental-autoimmune-uveitis-and-complement-activation-in-rats
#1
Dadong Guo, Bing Hu, Hongying Tang, Yuanyuan Sun, Bin Liu, Qingmei Tian, Hongsheng Bi
Uveitis is an autoimmune disease that usually damages the vision function, leading to poor visual quality in patients. As an autoimmune ocular inflammatory disease, the pathogenesis of uveitis is associated with abnormal expression of some proteins and aberrant regulation of multiple signaling pathways. Nevertheless, the detailed mechanism remains unclear. In this study, we induced an experimental autoimmune uveitis (EAU) model in rats. We determined the levels of C3a and membrane attack complex C5b-9 (soluble C5b-9, sC5b-9) in both plasma and aqueous humor, identified the differentially expressed proteins in plasma by liquid chromatography-tandem mass spectrometry, and employed bioinformatics algorithms to analyze differentially expressed proteins in EAU rat plasma...
February 15, 2017: Scandinavian Journal of Immunology
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
#2
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/28115367/lgl-leukemia-from-pathogenesis-to-treatment
#3
Thierry Lamy, Aline Moignet, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia has been recognized by the WHO classifications among mature T cell and NK cell neoplasms. There are 3 categories: chronic T cell leukemia and NK cell lymphocytosis which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, Pi3k-Akt, RasRaf-1, MEK1/ERK, sphingolipid, and NFκB...
January 23, 2017: Blood
https://www.readbyqxmd.com/read/28112970/clinical-use-of-pi3k-inhibitors-in-b-cell-lymphoid-malignancies-today-and-tomorrow
#4
I B Greenwell, C R Flowers, K A Blum, J B Cohen
PI3K inhibitors are an important new therapeutic option for the treatment of relapsed and refractory B-cell lymphoid malignancies. Idelalisib is a PI3Kδ inhibitor that has been approved for the treatment of lymphoma and chronic lymphocytic leukemia in the relapsed/refractory setting, and several other PI3K inhibitors are being developed targeting other isoforms of the PI3K enzyme, which results in distinct toxicities and variable efficacy in the clinical setting. Areas covered: We provide a general overview of PI3K inhibitors, recommended applications, and the mechanism and management of toxicities...
March 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28100106/systemic-lupus-erythematosus-in-the-light-of-the-regulatory-effects-of-galectin-1-on-t-cell-function
#5
Á Hornung, É Monostori, L Kovács
Galectin-1 is an endogenous immunoregulatory lectin-type protein. Its most important effects are the inhibition of the differentiation and cytokine production of Th1 and Th17 cells, and the induction of apoptosis of activated T-cells. Galectin-1 has been identified as a key molecule in antitumor immune surveillance, and data are accumulating about the pathogenic role of its deficiency, and the beneficial effects of its administration in various autoimmune disease models. Initial animal and human studies strongly suggest deficiencies in both galectin-1 production and responsiveness in systemic lupus erythematosus (SLE) T-cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28081180/pi3k%C3%AE-deficient-nod-mice-are-protected-from-diabetes-by-restoring-the-balance-of-regulatory-to-effector-t-cells
#6
Jamil Azzi, Lindsay Thueson, Robert Moore, Rozita Abdoli, Helena Reijonen, Reza Abdi
With a steady increase in its incidence and lack of curative treatment, type 1 diabetes (T1D) has emerged as a major health problem worldwide. To design novel effective therapies, there is a pressing need to identify regulatory targets controlling the balance of autoreactive to regulatory-T-cells (Tregs). We previously showed that the inhibition of the γ-subunit of the Phosphoinositide-3-kinase (PI3K), significantly suppress autoimmune-diabetes. To further delineate the mechanisms and the selectivity of specific immune modulation by PI3Kγ-inhibition, we developed a new NOD mouse model of T1D lacking the γ-subunit of PI3K...
2017: PloS One
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#7
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28061982/pi3k-signaling-pathway-in-normal-b-cells-and-indolent-b-cell-malignancies
#8
REVIEW
Georgios Pongas, Bruce D Cheson
In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs), B-cell receptor signaling leads to activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Idelalisib, a PI3Kδ inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single-agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and relapsed follicular lymphoma (FL)...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28057547/intracellular-signaling-modifications-involved-in-the-anti-inflammatory-effect-of-4-alkoxy-6-9-dichloro-1-2-4-triazolo-4-3-a-quinoxalines-on-macrophages
#9
Antonio J Ruiz-Alcaraz, María Tristán-Manzano, Antonio Guirado, Jesús Gálvez, María Martínez-Esparza, Pilar García-Peñarrubia
Inflammation is part of a complex biological response directed by the immune system to fight pathogens and maintain homeostasis. Dysregulation of the inflammatory process leads to development of chronic inflammatory or autoimmune diseases. Several cell types, such as macrophages, and cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) are involved in the regulation of inflammation. The important role played by these cytokines as mediators of the inflammatory process and the side effects of current therapies have promoted the search of new therapeutic alternatives...
March 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28026003/quercetin-promotes-the-apoptosis-of-fibroblast-like-synoviocytes-in-rheumatoid-arthritis-by-upregulating-lncrna%C3%A2-malat1
#10
Fang Pan, Lihua Zhu, Haozhe Lv, Chunpeng Pei
Rheumatoid arthritis (RA) is a chronic autoimmune joint disease and fibroblast-like synoviocytes (FLS) are the resident mesenchymal cells of synovial joints. Quercetin is a dietary antioxidant. In this study, we aimed to explore the mechanisms responsible for the quercetin-induced apoptosis of FLS from patients with RA (termed RAFLS). RAFLS viability was determined following treatent of the cells with or without quercetin using the Cell Counting kit-8 (CCK-8) assay. The apoptosis of the RAFLS was analyzed using the Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit I...
November 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28011648/foxo4-and-stat3-dependent-il-10-production-by-progranulin-in-regulatory-t-cells-restrains-inflammatory-arthritis
#11
Wenyu Fu, Wenhuo Hu, Lei Shi, Jyoti Joshi Mundra, GuoZhi Xiao, Michael L Dustin, Chuan-Ju Liu
Progranulin (PGRN) restrains inflammation and is therapeutic against inflammatory arthritis; however, the underlying immunological mechanism remains unknown. In this study, we demonstrated that anti-inflammatory cytokine IL-10 was a critical mediator for PGRN-mediated anti-inflammation in collagen-induced arthritis by using PGRN and IL-10 genetically modified mouse models. IL-10 green fluorescent protein reporter mice revealed that regulatory T (Treg) cells were the predominant source of IL-10 in response to PGRN...
December 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27951586/nlrc3-is-an-inhibitory-sensor-of-pi3k-mtor-pathways-in-cancer
#12
Rajendra Karki, Si Ming Man, R K Subbarao Malireddi, Sannula Kesavardhana, Qifan Zhu, Amanda R Burton, Bhesh Raj Sharma, Xiaopeng Qi, Stephane Pelletier, Peter Vogel, Philip Rosenstiel, Thirumala-Devi Kanneganti
NLRs (nucleotide-binding domain and leucine-rich repeats) belong to a large family of cytoplasmic sensors that regulate an extraordinarily diverse range of biological functions. One of these functions is to contribute to immunity against infectious diseases, but dysregulation of their functional activity leads to the development of inflammatory and autoimmune diseases. Cytoplasmic innate immune sensors, including NLRs, are central regulators of intestinal homeostasis. NLRC3 (also known as CLR16.2 or NOD3) is a poorly characterized member of the NLR family and was identified in a genomic screen for genes encoding proteins bearing leucine-rich repeats (LRRs) and nucleotide-binding domains...
December 12, 2016: Nature
https://www.readbyqxmd.com/read/27890794/target-regulation-of-pi3k-akt-mtor-pathway-by-cannabidiol-in-treatment-of-experimental-multiple-sclerosis
#13
Sabrina Giacoppo, Federica Pollastro, Gianpaolo Grassi, Placido Bramanti, Emanuela Mazzon
This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found to be activated by cannabinoids in several immune and non-immune cells, currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55...
January 2017: Fitoterapia
https://www.readbyqxmd.com/read/27798164/programmed-death-ligand-1-plays-a-neuroprotective-role-in-experimental-autoimmune-neuritis-by-controlling-peripheral-nervous-system-inflammation-of-rats
#14
Yanan Ding, Ranran Han, Wei Jiang, Jinting Xiao, Haijie Liu, Xiuju Chen, Xiaowen Li, Junwei Hao
Programmed death 1 (PD-1; CD279), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for T cell dysfunction in infectious diseases and cancers. The ligand for PD-1, programmed death ligand 1 (PD-L1; also known as B7-H1, CD274), is a member of the B7 family. The engagement of PD-1 with programmed death ligand can downregulate autoreactive T cells that participate in multiple autoimmune diseases. Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome, and the pathogenesis of EAN is mediated principally through T cells and macrophages...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27791035/mirna92a-targets-klf2-and-the-phosphatase-pten-signaling-to-promote-human-t-follicular-helper-precursors-in-t1d-islet-autoimmunity
#15
Isabelle Serr, Rainer W Fürst, Verena B Ott, Martin G Scherm, Alexei Nikolaev, Füsun Gökmen, Stefanie Kälin, Stephanie Zillmer, Melanie Bunk, Benno Weigmann, Nicole Kunschke, Brigitta Loretz, Claus-Michael Lehr, Benedikt Kirchner, Bettina Haase, Michael Pfaffl, Ari Waisman, Richard A Willis, Anette-G Ziegler, Carolin Daniel
Aberrant immune activation mediated by T effector cell populations is pivotal in the onset of autoimmunity in type 1 diabetes (T1D). T follicular helper (TFH) cells are essential in the induction of high-affinity antibodies, and their precursor memory compartment circulates in the blood. The role of TFH precursors in the onset of islet autoimmunity and signaling pathways regulating their differentiation is incompletely understood. Here, we provide direct evidence that during onset of islet autoimmunity, the insulin-specific target T-cell population is enriched with a C-X-C chemokine receptor type 5 (CXCR5)(+)CD4(+) TFH precursor phenotype...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27762043/tlr4-induced-b7-h1-on-keratinocytes-negatively-regulates-cd4-t-cells-and-cd8-t-cells-responses-in-oral-lichen-planus
#16
Jing Zhang, Ya-Qin Tan, Ming-Hui Wei, Xiao-Jing Ye, Guan-Ying Chen, Rui Lu, Ge-Fei Du, Gang Zhou
Oral lichen planus (OLP) is a T-cell-mediated autoimmune mucocutaneous disease affected by the interactions among the keratinocytes, CD4(+) T cells and CD8(+) T cells. B7-H1 induced by Toll-like receptors (TLRs), can suppress T cell immune reaction, thereby resulting in immune tolerance. However, the role of TLRs-mediated B7-H1 on keratinocytes in the immune response of OLP is still unknown. The present study showed that TLR4 could induce time-coursed B7-H1 expression on oral keratinocytes, and blocking NF-κB or PI3K/mTOR pathway down-regulated B7-H1 transcriptional expression...
October 20, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27739372/phosphoinositide-3-kinases-as-the-novel-therapeutic-targets-for-the-inflammatory-diseases-current-and-future-perspectives
#17
Preeti Vyas, Divya Vohora
Recent findings have publicized phosphoinositide-3-kinases (PI3Ks) as novel therapeutic targets, which are also purported to be involved in the complex pathophysiology of inflammatory and various other diseases. They are recognized to participate in the inflammatory cellular responses by modulating the growth, development and proliferation of various immune cells and hence, affect the release of various cytokines and other inflammatory mediators involved in these manifestations. The review presents a brief synopsis of the PI3K/AKT/mTOR signalling pathway along with the current and future prospects of targeting PI3Ks for various diseases, like malignant, autoimmune, inflammatory, cardiovascular, neurological disorders etc...
October 13, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27729613/microrna-126-affects-rheumatoid-arthritis-synovial-fibroblast-proliferation-and-apoptosis-by-targeting-pik3r2-and-regulating-pi3k-akt-signal-pathway
#18
Yuan Qu, Jing Wu, Jia-Xin Deng, Yu-Ping Zhang, Wan-Yi Liang, Zhen-Lan Jiang, Qing-Hong Yu, Juan Li
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints as well as an increased risk of cardiovascular disease. RA synovial fibroblasts (RASFs) are involved in the progression of RA and release pro-inflammatory cytokines. On the other hand, microRNAs (miRs) may help control the inflammatory response of immune and non-immune cells. Therefore, our study used lentiviral expression vectors to test the effects of miR-126 overexpression on RASF proliferation and apoptosis...
October 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27671821/celastrol-and-its-role-in-controlling%C3%A2-chronic-diseases
#19
Shivaprasad H Venkatesha, Kamal D Moudgil
Celastrol, a triterpenoid derived from traditional Chinese medicinal plants, has anti-inflammatory, antioxidant, and anticancer activities. Celastrol has shown preventive/therapeutic effects in experimental models of several chronic diseases. These include, chronic inflammatory and autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and psoriasis), neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis), atherosclerosis, obesity, Type 2 diabetes, and cancer...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27671108/antigen-specific-immune-modulation-targets-mtorc1-function-to-drive-chemokine-receptor-mediated-t-cell-tolerance
#20
Weirong Chen, Xiaoxiao Wan, Tobechukwu K Ukah, Mindy M Miller, Subhasis Barik, Alexis N Cattin-Roy, Habib Zaghouani
To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells...
November 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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