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PI3K AND SLE

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https://www.readbyqxmd.com/read/27665947/contribution-and-underlying-mechanisms-of-cxcr4-overexpression-in-patients-with-systemic-lupus-erythematosus
#1
Li-Dan Zhao, Di Liang, Xiang-Ni Wu, Yang Li, Jing-Wen Niu, Chen Zhou, Li Wang, Hua Chen, Wen-Jie Zheng, Yun-Yun Fei, Fu-Lin Tang, Yong-Zhe Li, Feng-Chun Zhang, Wei He, Xue-Tao Cao, Xuan Zhang
Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected...
September 26, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/26277892/ligation-of-cd180-inhibits-ifn-%C3%AE-signaling-in-a-lyn-pi3k-btk-dependent-manner-in-b-cells
#2
Ming You, Guanjun Dong, Fanlin Li, Feiya Ma, Jing Ren, Yujun Xu, Huimin Yue, Ruijing Tang, Deshan Ren, Yayi Hou
A hallmark of systemic lupus erythematosus (SLE) is the consistent production of various auto-antibodies by auto-reactive B cells. Interferon-α (IFN-α) signaling is highly activated in SLE B cells and plays a vital role in the antibody response by B cells. Previous studies have shown that CD180-negative B cells, which are dramatically increased in SLE patients, are responsible for the production of auto-antibodies. However, the association between CD180 and IFN-α signaling remains unknown. In the present study, we explored the effect of CD180 on regulating the activation of IFN-α signaling in B cells...
August 17, 2015: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/26030228/microrna-regulation-of-lymphocyte-tolerance-and-autoimmunity
#3
REVIEW
Laura J Simpson, K Mark Ansel
Understanding the cell-intrinsic cues that permit self-reactivity in lymphocytes, and therefore autoimmunity, requires an understanding of the transcriptional and posttranscriptional regulation of gene expression in these cells. In this Review, we address seminal and recent research on microRNA (miRNA) regulation of central and peripheral tolerance. Human and mouse studies demonstrate that the PI3K pathway is a critical point of miRNA regulation of immune cell development and function that affects the development of autoimmunity...
June 2015: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/25989537/leptin-and-neutrophil-activating-peptide-2-promote-mesenchymal-stem-cell-senescence-through-activation-of-the-phosphatidylinositol-3-kinase-akt-pathway-in-patients-with-systemic-lupus-erythematosus
#4
Haifeng Chen, Bingyu Shi, Xuebing Feng, Wei Kong, Weiwei Chen, Linyu Geng, Jinyun Chen, Rui Liu, Xia Li, WanJun Chen, Xiang Gao, Lingyun Sun
OBJECTIVE: Mesenchymal stem cells (MSCs) derived from patients with systemic lupus erythematosus (SLE) exhibit enhanced senescence. Cellular senescence has been reported to be induced by several inflammatory cytokines, including interferon-α (IFNα) and IFNγ, that are involved in the pathogenesis of SLE. We undertook this study to investigate whether the inflammatory environment in SLE could affect MSC senescence. METHODS: Cellular senescence was measured by staining of senescence-associated β-galactosidase and by expression of the cell cycle inhibitors p53 and p21...
September 2015: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/25989067/a-50-year-old-woman-with-cowden-syndrome-and-joint-pains
#5
Vinay Sagar, Jeffrey R Bond, Vaidehi R Chowdhary
No abstract text is available yet for this article.
November 2015: Arthritis Care & Research
https://www.readbyqxmd.com/read/25909640/infection-of-female-bwf1-lupus-mice-with-malaria-parasite-attenuates-b-cell-autoreactivity-by-modulating-the-cxcl12-cxcr4-axis-and-its-downstream-signals-pi3k-akt-nf%C3%AE%C2%BAb-and-erk
#6
Gamal Badr, Ayat Sayed, Mostafa A Abdel-Maksoud, Amany O Mohamed, Azza El-Amir, Fathy A Abdel-Ghaffar, Saleh Al-Quraishy, Mohamed H Mahmoud
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis...
2015: PloS One
https://www.readbyqxmd.com/read/25149466/complement-component-c5a-permits-the-coexistence-of-pathogenic-th17-cells-and-type-i-ifn-in-lupus
#7
Sudesh Pawaria, Kritika Ramani, Kelly Maers, Youhua Liu, Lawrence P Kane, Marc C Levesque, Partha S Biswas
Systemic lupus erythematosus (SLE) is a type I IFN (IFN-I)-driven autoimmune disorder with exaggerated B and Th cell responses. Th17 cells, a recently identified Th cell subset, have been strongly implicated in the pathogenesis of SLE. Because IFN-I suppresses the generation and expansion of Th17 cells in an IL-27-dependent manner, it is unclear how pathogenic Th17 cells are generated in SLE in the presence of an environment characterized by high IFN-I levels. In this study, we showed that activation of c5aR on murine macrophages blocked IFN-I-mediated IL-27 production, thus permitting the development of Th17 cells...
October 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24953795/effect-of-st3gal-4-and-fut-7-on-sialyl-lewis-x-synthesis-and-multidrug-resistance-in-human-acute-myeloid-leukemia
#8
COMPARATIVE STUDY
Hongye Ma, Huimin Zhou, Peng Li, Xiaobo Song, Xiaoyan Miao, Yanping Li, Li Jia
Sialyl Lewis X (sLe X, CD15s) is a key antigen produced on tumor cell surfaces during multidrug resistance (MDR) development. The present study investigated the effect of α1, 3 fucosyltransferase VII (FucT VII) and α2, 3 sialyltransferase IV (ST3Gal IV) on sLe X oligosaccharides synthesis as well as their impact on MDR development in acute myeloid leukemia cells (AML). FUT7 and ST3GAL4 were overexpressed in three AML MDR cells and bone marrow mononuclear cells (BMMC) of AML patients with MDR by real-time polymerase chain reaction (PCR)...
September 2014: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/24935930/inhibition-of-pi3k%C3%AE-reduces-kidney-infiltration-by-macrophages-and-ameliorates-systemic-lupus-in-the-mouse
#9
Abel Suárez-Fueyo, José M Rojas, Ariel E Cariaga, Esther García, Bart H Steiner, Domingo F Barber, Kamal D Puri, Ana C Carrera
Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease generated and maintained throughout life by autoreactive T and B cells. Class I phosphoinositide 3-kinases (PI3K) are heterodimers composed of a regulatory and a catalytic subunit that catalyze phosphoinositide-3,4,5-P3 formation and regulate cell survival, migration, and division. Activity of the PI3Kδ isoform is enhanced in human SLE patient PBLs. In this study, we analyzed the effect of inhibiting PI3Kδ in MRL/lpr mice, a model of human SLE...
July 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24904582/characterization-of-novel-pi3k%C3%AE-inhibitors-as-potential-therapeutics-for-sle-and-lupus-nephritis-in-pre-clinical-studies
#10
Philipp Haselmayer, Montserrat Camps, Mathilde Muzerelle, Samer El Bawab, Caroline Waltzinger, Lisa Bruns, Nada Abla, Mark A Polokoff, Carole Jond-Necand, Marilène Gaudet, Audrey Benoit, Dominique Bertschy Meier, Catherine Martin, Denise Gretener, Maria Stella Lombardi, Roland Grenningloh, Christoph Ladel, Jørgen Søberg Petersen, Pascale Gaillard, Hong Ji
SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human...
2014: Frontiers in Immunology
https://www.readbyqxmd.com/read/24790152/through-an-itim-independent-mechanism-the-fc%C3%AE-riib-blocks-b-cell-activation-by-disrupting-the-colocalized-microclustering-of-the-b-cell-receptor-and-cd19
#11
Liling Xu, Gen Li, Jing Wang, Yilin Fan, Zhengpeng Wan, Shaosen Zhang, Samina Shaheen, Jing Li, Li Wang, Cai Yue, Yan Zhao, Fei Wang, Joseph Brzostowski, Ying-Hua Chen, Wenjie Zheng, Wanli Liu
B cell activation is regulated through the interplay of the BCR with the inhibitory coreceptor FcγRIIB and the activating coreceptor CD19. Recent studies suggest that Ag-driven BCR microclusters are efficiently converted to a signaling active state on colocalization with CD19 microclusters. Using total internal reflection fluorescence microscopy-based, high-resolution, high-speed live-cell and molecule imaging approaches, we show that when co-ligated to the BCR, the FcγRIIB can inhibit B cell activation by blocking the colocalization of BCR and CD19 microclusters within the B cell immunological synapse...
June 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24477292/p85%C3%AE-recruitment-by-the-cd300f-phosphatidylserine-receptor-mediates-apoptotic-cell-clearance-required-for-autoimmunity-suppression
#12
Linjie Tian, Seung-Chul Choi, Yousuke Murakami, Joselyn Allen, Herbert C Morse, Chen-Feng Qi, Konrad Krzewski, John E Coligan
Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K)...
2014: Nature Communications
https://www.readbyqxmd.com/read/24445960/inhibition-of-pi3k%C3%AE-improves-systemic-lupus-in-mice
#13
Yanxia Wang, Lei Zhang, Ping Wei, Huailiang Zhang, Cuijie Liu
Systemic lupus erythematosus (SLE) is an autoimmune disease accompanying excessive inflammatory responses. Phosphoinositide 3-kinase p110δ (PI3Kδ) is reported to associate with autoimmune conditions. We here aimed to determine whether selective inhibition of PI3Kδ is effective in a lupus model of BXSB mice, using the selective PI3Kδ inhibitor IC87114, which was intraperitoneally administrated to BXSB mice aged from 14 to 22 weeks. We showed that IC87114 improved renal function by decreasing the levels of proteinuria and serum creatinine, ameliorating the pathologic changes of kidneys and IgG and C3 deposition...
June 2014: Inflammation
https://www.readbyqxmd.com/read/24211136/pi3k-%C3%AE-and-pi3k-%C3%AE-inhibition-by-ipi-145-abrogates-immune-responses-and-suppresses-activity-in-autoimmune-and-inflammatory-disease-models
#14
David G Winkler, Kerrie L Faia, Jonathan P DiNitto, Janid A Ali, Kerry F White, Erin E Brophy, Melissa M Pink, Jennifer L Proctor, Jennifer Lussier, Christian M Martin, Jennifer G Hoyt, Bonnie Tillotson, Erin L Murphy, Alice R Lim, Brian D Thomas, John R Macdougall, Pingda Ren, Yi Liu, Lian-Sheng Li, Katti A Jessen, Christian C Fritz, Joi L Dunbar, James R Porter, Christian Rommel, Vito J Palombella, Paul S Changelian, Jeffery L Kutok
Phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ are preferentially expressed in immune cells, and inhibitors targeting these isoforms are hypothesized to have anti-inflammatory activity by affecting the adaptive and innate immune response. We report on a potent oral PI3K-δ and PI3K-γ inhibitor (IPI-145) and characterize this compound in biochemical, cellular, and in vivo assays. These studies demonstrate that IPI-145 exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation...
November 21, 2013: Chemistry & Biology
https://www.readbyqxmd.com/read/23970345/progesterone-protects-ovarian-cancer-cells-from-cisplatin-induced-inhibitory-effects-through-progesterone-receptor-membrane-component-1-2-as-well-as-akt-signaling
#15
Xiaofei Zhu, Yue Han, Zhuyuan Fang, Wenzhong Wu, Mingde Ji, Fengmeng Teng, Wei Zhu, Xuewen Yang, Xuemei Jia, Chunbing Zhang
Progesterone, also known as P4 (pregn-4-ene-3, 20-dione), is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Despite the physiological effects, P4 is also effective for the treatment of numerous pathological states, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus as well as cancer. Considering the hormone microenvironment of gynecological cancers, P4 should be particularly noted in ovarian cancer...
November 2013: Oncology Reports
https://www.readbyqxmd.com/read/23028409/the-therapeutic-potential-for-pi3k-inhibitors-in-autoimmune-rheumatic-diseases
#16
Edward Banham-Hall, Menna R Clatworthy, Klaus Okkenhaug
The class 1 PI3Ks are lipid kinases with key roles in cell surface receptor-triggered signal transduction pathways. Two isoforms of the catalytic subunits, p110γ and p110δ, are enriched in leucocytes in which they promote activation, cellular growth, proliferation, differentiation and survival through the generation of the second messenger PIP3. Genetic inactivation or pharmaceutical inhibition of these PI3K isoforms in mice result in impaired immune responses and reduced susceptibility to autoimmune and inflammatory conditions...
2012: Open Rheumatology Journal
https://www.readbyqxmd.com/read/22537464/attenuation-of-phosphoinositide-3-kinase-%C3%AE-signaling-restrains-autoimmune-disease
#17
Mhairi J Maxwell, Evelyn Tsantikos, Anne M Kong, Bart Vanhaesebroeck, David M Tarlinton, Margaret L Hibbs
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by the production of autoantibodies against nuclear components. Lyn-deficient mice are an excellent animal model of SLE manifesting clinical, pathological and biochemical features seen in the human disease. They develop autoreactive antibodies, glomerulonephritis and show generalized inflammation, and their B cells have a hyperactive phenotype. Since loss of Lyn confers hyper-activation of phosphoinositide 3-kinase (PI3K) signaling, we studied the effect of down-modulating PI3K in Lyn-deficient mice...
June 2012: Journal of Autoimmunity
https://www.readbyqxmd.com/read/22375903/enhanced-apoptosis-and-senescence-of-bone-marrow-derived-mesenchymal-stem-cells-in-patients-with-systemic-lupus-erythematosus
#18
Xia Li, Lei Liu, Defang Meng, Dandan Wang, Jiyun Zhang, Dongyan Shi, Huiqing Liu, Huji Xu, Liwei Lu, Lingyun Sun
Previous studies indicated that bone marrow mesenchymal stem cells (BMSCs) from patients with systemic lupus erythematosus (SLE) exhibited impaired capacities of proliferation, differentiation, secretion of cytokines, and immune modulation. In this study, we aimed to investigate whether apoptosis and senescence of SLE BMSCs were dysregulated. We found that there were increased frequencies of apoptotic and aging SLE BMSCs in comparison with those of normal controls. Notably, levels of Bcl-2 expression in SLE BMSCs were markedly decreased both at mRNA and protein levels...
September 1, 2012: Stem Cells and Development
https://www.readbyqxmd.com/read/22374437/-recent-findings-on-phosphoinositide-3-kinase-in-rheumatic-diseases
#19
REVIEW
Naoto Tamura
Rheumatic diseases are chronic inflammatory disorders, and many of them are autoimmune diseases. Class I phosphatidylinositol-3 kinases (PI3Ks) are enzymes that phosphorylate phosphoinositides in response to extracellular stimuli and regulates cellular activation, proliferation, and migration, in a variety of cell types, suggesting that they play critical roles in the development of inflammation. In patients with rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), recent reports have shown convincing pathogenic evidence for the involvement of PI3K/Akt signaling pathways in chronic inflammation...
2012: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/22155250/functional-analysis-of-%C3%AE-1-3-4-fucosyltransferase-vi-in-human-hepatocellular-carcinoma-cells
#20
Qiya Guo, Bin Guo, Yingming Wang, Jun Wu, Wenjun Jiang, Shenan Zhao, Shouyi Qiao, Yanhua Wu
The α1,3/4-fucosyltransferases (FUT) subfamily are key enzymes in cell surface antigen synthesis during various biological processes. A novel role of FUTs in tumorigenesis has been discovered recently, however, the underlying mechanism remains largely unknown. Here, we characterized FUT6, a member of α1,3/4-FUT subfamily, in human hepatocellular carcinoma (HCC). In HCC tissues, the expression levels of FUT6 and its catalytic product SLe(x) were significantly up-regulated. Overexpression of FUT6 in HCC cells enhanced S-phase cell population, promoted cell growth and colony formation ability...
January 6, 2012: Biochemical and Biophysical Research Communications
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