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pi3k AND autoimmune

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https://www.readbyqxmd.com/read/28100106/systemic-lupus-erythematosus-in-the-light-of-the-regulatory-effects-of-galectin-1-on-t-cell-function
#1
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
#2
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
#3
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...
January 6, 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
#4
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
#5
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...
January 3, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/27639182/effects-of-kinsenoside-a-potential-immunosuppressive-drug-for-autoimmune-hepatitis-on-dendritic-cells-cd8-t-cells-communication-in-mice
#17
Ming Xiang, Tingting Liu, Wanyue Tan, Hongyu Ren, Hua Li, Junjun Liu, Hui Cao, Qi Cheng, Xiulan Liu, Hucheng Zhu, Yali Tuo, Jianping Wang, Yonghui Zhang
: The central purpose of this study was to investigate therapeutic effects of the botanical derivative, kinsenoside (KD), in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and proinflammatory cytokines, in concanavalin A-induced T-cell-mediated hepatitis, and in dendritic cells (DCs) loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8(+) T cell sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27637385/bullous-pemphigoid-outcome-is-associated-with-cxcl10-induced-matrix-metalloproteinase-9-secretion-from-monocytes-and-neutrophils-but-not-lymphocytes
#18
Meriem Riani, Sébastien Le Jan, Julie Plée, Anne Durlach, Richard Le Naour, Guy Haegeman, Philippe Bernard, Frank Antonicelli
BACKGROUND: The outcome of bullous pemphigoid (BP), the most frequent autoimmune skin-blistering disease, involves matrix metalloproteinase 9 (MMP-9), IL-17, and IL-23 release from infiltrated inflammatory cells. The chemokine CXCL10 has been associated with several autoimmune diseases, but its participation in BP pathophysiology still needs to be clarified. OBJECTIVE: We sought to assess whether BP outcome was associated with different CXCL10 levels and to evaluate the contribution of CXCL10 to the described cytokine/protease inflammatory loop associated with disease outcome...
September 13, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27477328/immune-dysregulation-in-patients-with-pten-hamartoma-tumor-syndrome-analysis-of-foxp3-regulatory-t%C3%A2-cells
#19
Hannah H Chen, Norman Händel, Joanne Ngeow, James Muller, Michael Hühn, Huei-Ting Yang, Mario Heindl, Roos-Marijn Berbers, Ahmed N Hegazy, Janina Kionke, Lamis Yehia, Ulrich Sack, Frank Bläser, Anne Rensing-Ehl, Julia Reifenberger, Julia Keith, Simon Travis, Andreas Merkenschlager, Wieland Kiess, Christian Wittekind, Lisa Walker, Stephan Ehl, Stefan Aretz, Michael L Dustin, Charis Eng, Fiona Powrie, Holm H Uhlig
BACKGROUND: Patients with heterozygous germline mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) experience autoimmunity and lymphoid hyperplasia. OBJECTIVES: Because regulation of the phosphoinositide 3-kinase (PI3K) pathway is critical for maintaining regulatory T (Treg) cell functions, we investigate Treg cells in patients with heterozygous germline PTEN mutations (PTEN hamartoma tumor syndrome [PHTS]). METHODS: Patients with PHTS were assessed for immunologic conditions, lymphocyte subsets, forkhead box P3 (FOXP3)(+) Treg cell levels, and phenotype...
June 18, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27405597/methane-limit-lps-induced-nf-%C3%AE%C2%BAb-mapks-signal-in-macrophages-and-suppress-immune-response-in-mice-by-enhancing-pi3k-akt-gsk-3%C3%AE-mediated-il-10-expression
#20
Xu Zhang, Na Li, Han Shao, Yan Meng, Liping Wang, Qian Wu, Ying Yao, Jinbao Li, Jinjun Bian, Yan Zhang, Xiaoming Deng
Inflammatory diseases such as sepsis and autoimmune colitis, characterized by an overwhelming activation of the immune system and the counteracting anti-inflammatory response, remain a major health problem in worldwide. Emerging evidence suggests that methane have a protective effect on many animal models, like ischaemia reperfusion injury and diabetes-associated diseases. Whether methane could modulating inflammatory diseases remains largely unknown. Here we show that methane-rich saline (MS) ip treatment (16 ml/kg) alleviated endotoxin shock, bacteria-induced sepsis and dextran-sulfate-sodium-induced colitis in mice via decreased production of TNF-α and IL-6...
2016: Scientific Reports
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