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https://www.readbyqxmd.com/read/28544564/podocyte-activation-of-nlrp3-inflammasomes-contributes-to-the-development-of-proteinuria-in-lupus-nephritis
#1
Rong Fu, Chaohuan Guo, Shuang Wang, Yuefang Huang, Ou Jin, Haoqiang Hu, Jingxian Chen, Bihua Xu, Mianjing Zhou, Jijun Zhao, Sun-Sang J Sung, Hongyang Wang, Felicia Gaskin, Niansheng Yang, Shu-Man Fu
Objective Development of proteinuria in lupus nephritis (LN) is associated with podocyte dysfunction. The NLRP3 inflammasome has been implicated in the pathogenesis of LN. This study investigates whether NLRP3 inflammasome activation is involved in the development of podocyte injury in LN. Methods A fluorescence-labeled caspase-1 inhibitor probe was used to detect the activation of NLRP3 inflammasomes in podocytes in lupus-prone NZM2328 mice and in renal biopsies from LN patients. MCC950, a selective inhibitor of NLRP3, was used to treat NZM2328 mice...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28544067/vitamin-d3-alters-the-expression-of-toll-like-receptors-in-peripheral-blood-mononuclear-cells-of-patients-with-systemic-lupus-erythematosus
#2
Esmaeil Yazdanpanah, Mahmoud Mahmoudi, Maryam Sahebari, Zahra Rezaieyazdi, Seyed-Alireza Esmaeili, Nafiseh Tabasi, Soheila Jaberi, Amirhossein Sahebkar, Maryam Rastin
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of inflammatory cytokines and autoreactive antibodies due to the loss of immune tolerance. Recognition of self-nucleic acids by intracellular Toll-like receptors (TLRs) can overactivate immune responses and this abnormal activation of TLRs contributes to the pathogenesis of the disease. In recent years, anti-inflammatory and immunomodulatory effects of 1, 25-dihydroxyvitamin D3 (VitD3) on the immune system has received particular attention...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28539924/therapeutic-development-of-mesenchymal-stem-cells-or-their-extracellular-vesicles-to-inhibit-autoimmune-mediated-inflammatory-processes-in-systemic-lupus-erythematosus
#3
REVIEW
Juhi Sharma, Jeffrey M Hampton, Giancarlo R Valiente, Takuma Wada, Holly Steigelman, Matthew C Young, Rachel R Spurbeck, Alisa D Blazek, Steffi Bösh, Wael N Jarjour, Nicholas A Young
Since being discovered over half a century ago, mesenchymal stem cells (MSCs) have been investigated extensively to characterize their cellular and physiological influences. MSCs have been shown to possess immunosuppressive capacity through inhibiting lymphocyte activation/proliferation and proinflammatory cytokine secretion while simultaneously demonstrating limited allogenic reactivity, which subsequently led to the evaluation of therapeutic feasibility to treat inflammatory diseases. Although regulatory constraints have restricted MSC development pharmacologically, limited clinical studies have shown encouraging results using MSC infusions to treat systemic lupus erythematosus (SLE); but, more trials will have to be performed to conclusively determine the clinical efficacy of MSCs to treat SLE...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28539549/the-metabolic-regulation-in-immune-cells-and-pathogenesis-of-systemic-lupus-erythematosus-%C3%A2-toward-new-therapeutic-applications%C3%A2
#4
Yusuke Takeshima, Yukiko Iwasaki, Tomohisa Okamura, Keishi Fujio, Kazuhiko Yamamoto
  The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28535641/-effect-of-interleukin-6-promoter-dna-methylation-on-the-pathogenesis-of-systemic-lupus-erythematosus
#5
X Y Cai, Y Lu, C Tang, X J Lin, J H Ye, W N Li, Z X He, F F Li
Objective: To analyze peripheral blood interleukin-6 (IL-6) promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). Methods: Blood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed...
May 23, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28534426/the-immunological-personality-of-close-relatives-of-sle-patients
#6
M R Salaman, D A Isenberg
Immunological abnormalities seen in relatives of patients with autoimmune disorders can be useful in understanding the pathogenesis of the disease since, unlike in patients, they cannot result from the disease process or drug treatment. In this article we present a brief overview of our studies of the basic immunological status of close relatives of SLE patients. We looked at blood levels of IgG, IgM and antibodies to double-stranded DNA, as well as at NK cell numbers and cytotoxic activity and the levels of NKT, B and T cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28530841/the-increased-expression-of-toll-like-receptor-4-in-renal-and-skin-lesions-in-lupus-erythematosus
#7
Nesrine Elloumi, Raouia Fakhfakh, Lobna Ayadi, Khadija Sellami, Olfa Abida, Mariem Ben Jmaa, Tahya Sellami, Khawla Kammoun, Hatem Masmoudi
Toll-like receptor 4 (TLR-4), a bacterial lipopolysaccharide sensor, is an innate immunity essential modulator. It is expressed on both immune and non-immune cells and may contribute to the cutaneous and renal manifestations during lupus erythematosus (LE). Our purpose is to evaluate TLR-4 expression and analyzing its role in lupus nephritis (LN) and chronic cutaneous lupus erythematosus (CLE) pathogenesis. TLR-4 immunohistochemical staining was performed on 30 LN renal biopsies compared with 11 healthy renal tissues and 30 skin biopsies from CLE patients compared with 15 normal individuals...
May 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28530463/association-of-il-6-174-g-c-polymorphism-with-the-risk-of-sle-among-south-indians-evidence-from-case-control-study-and-meta-analysis
#8
S K Katkam, L Rajasekhar, K Kumaraswami, V K Kutala
Cytokines play a direct role in disease pathogenesis of systemic lupus erythematosus (SLE). Elevated levels of serum IL-6 are well documented with the disease activity and anti-dsDNA antibodies in SLE. The 5' promoter region of the IL-6 gene has been shown to play a significant role in the regulation of gene expression. In view of this, the current study aimed to investigate the possible association of 5' promoter polymorphisms G-597A (rs1800797), G-572C (rs1800796) and G-174C (rs1800795) with the risk of SLE...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28525378/irf5-is-elevated-in-childhood-onset-sle-and-regulated-by-histone-acetyltransferase-and-histone-deacetylase-inhibitors
#9
Jin Shu, Ling Li, Lan-Bo Zhou, Jun Qian, Zhi-Dan Fan, Li-Li Zhuang, Lu-Lu Wang, Rui Jin, Hai-Guo Yu, Guo-Ping Zhou
Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523761/unraveling-the-expression-of-microrna-27a-nkg2d-in-peripheral-blood-mononuclear-cells-and-natural-killer-cells-of-pediatric-systemic-lupus-erythematosus-patients
#10
Shady K Sourour, Heba R Aboelenein, Noha M Elemam, Amira K Abdelhamid, Samia Salah, Ahmed I Abdelaziz
BACKGROUND AND AIM: The activity of natural killer (NK) cells is known to be decreased in systemic lupus erythematosus (SLE) patients. Nevertheless, the exact contribution of NK cells in the pathogenesis of SLE is still inconclusive. MicroRNAs (miRNAs), are small noncoding RNA molecules that play a fundamental role in regulating NK cell function. The objective of this study was to investigate the expression of miRNAs that might potentially target an essential activating receptor, NKG2D in peripheral blood mononuclear cells (PBMCs) and NK cells of SLE patients...
May 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28523301/large-variability-of-the-activity-and-chronicity-indexes-within-and-between-histological-classes-of-lupus-nephritis
#11
Tudor Azoicăi, Ioana Mădălina Belibou, Ludmila Lozneanu, Simona Eliza Giuşcă, Elena Cojocaru, Irina Draga Căruntu
Systemic lupus erythematosus (SLE) is characterized by a multifaceted pathogenesis and a heterogeneous clinical expression. The kidney involvement is almost unavoidable in all forms of SLE with chronic evolution, 75% of patients developing renal lesions defined as lupus nephritis (LN) - a glomerulonephritis with an extremely diverse lesion spectrum. The present study aimed to reevaluate a series of cases diagnosed as LN, focusing on the histological features in correlation with the level of activity and chronicity...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28520682/progress-in-the-pathogenesis-and-treatment-of-cardiac-manifestations-of-neonatal-lupus
#12
Peter Izmirly, Amit Saxena, Jill P Buyon
PURPOSE OF REVIEW: To provide new insights into pathogenesis, prevention and management of cardiac manifestations of neonatal lupus (cardiac neonatal lupus) and issues pertinent to all anti-SSA/Ro positive individuals of childbearing age. RECENT FINDINGS: Antibody specificity with high risk for cardiac neonatal lupus remains elusive, but high titers of Ro60, Ro52 or Ro52p200 antibodies appear to be required. Varying antibody specificities to the p200 region of Ro52 can induce first-degree block in a rodent model...
May 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28515990/topical-mycophenolate-mofetil-in-the-treatment-of-vitiligo-a-pilot-study
#13
Farhad Handjani, Shahin Aghaei, Iman Moezzi, Nasrin Saki
BACKGROUND: Vitiligo is a multifactorial disease that is characterized by circumscribed depigmented macules and patches. Autoimmune reactions may play an important role in the pathogenesis of the disease. Mycophenolate mofetil is a drug that inhibits DNA synthesis in lymphocytes and has been used in autoimmune diseases such as immunobullous skin diseases, lupus erythematosus, and autoimmune hepatitis. OBJECTIVES: The objective of this study was to show the efficacy of topical mycophenolate mofetil in the treatment of vitiligo...
April 2017: Dermatology Practical & Conceptual
https://www.readbyqxmd.com/read/28515366/experimental-lupus-is-aggravated-in-mouse-strains-with-impaired-induction-of-neutrophil-extracellular-traps
#14
Deborah Kienhöfer, Jonas Hahn, Julia Stoof, Janka Zsófia Csepregi, Christiane Reinwald, Vilma Urbonaviciute, Caroline Johnsson, Christian Maueröder, Malgorzata J Podolska, Mona H Biermann, Moritz Leppkes, Thomas Harrer, Malin Hultqvist, Peter Olofsson, Luis E Munoz, Attila Mocsai, Martin Herrmann, Georg Schett, Rikard Holmdahl, Markus H Hoffmann
Many effector mechanisms of neutrophils have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have been assigned a particularly detrimental role. Here we investigated the functional impact of neutrophils and NETs on a mouse model of lupus triggered by intraperitoneal injection of the cell death-inducing alkane pristane. Pristane-induced lupus (PIL) was aggravated in 2 mouse strains with impaired induction of NET formation, i.e., NOX2-deficient (Ncf1-mutated) and peptidyl arginine deiminase 4-deficient (PAD4-deficient) mice, as seen from elevated levels of antinuclear autoantibodies (ANAs) and exacerbated glomerulonephritis...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28506291/targeting-cd22-with-the-monoclonal-antibody-epratuzumab-modulates-human-b-cell-maturation-and-cytokine-production-in-response-to-toll-like-receptor-7-tlr7-and-b-cell-receptor-bcr-signaling
#15
Natalia V Giltiay, Geraldine L Shu, Anthony Shock, Edward A Clark
BACKGROUND: Abnormal B-cell activation is implicated in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell surface molecule CD22, which regulates activation through the B-cell receptor (BCR), is a potential target for inhibiting pathogenic B cells; however, the regulatory functions of CD22 remain poorly understood. In this study, we determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22 IgG1 monoclonal antibody, affects the activation of human B-cell subsets in response to Toll-like receptor 7 (TLR7) and BCR engagement...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28502135/systemic-lupus-erythmatosus-is-associated-with-disturbed-cytokine-milieu-and-increased-tnf-related-apoptosis-induced-ligand-levels
#16
Amal M Saeed, Mysara M Mogahed
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is cytotoxic to a wide variety of transformed cells, but not to most normal cells. This study measures serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and 10 and soluble TRAIL (sTRAIL) in patients with SLE and assesses their relation to severity of the disease. The study included 70 SLE patients and 20 healthy controls. Patients were diagnosed according to criteria proposed by the American Rheumatism Association for classification of SLE and disease activity was scored using the British Isles Lupus Assessment Group (BILAG-2004)...
June 2016: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/28500565/dysregulated-lymphoid-cell-populations-in-mouse-models-of-systemic-lupus-erythematosus
#17
REVIEW
Aurélie De Groof, Patrice Hémon, Olivier Mignen, Jacques-Olivier Pers, Edward K Wakeland, Yves Renaudineau, Bernard R Lauwerys
Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice...
May 13, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28490724/infection-in-systemic-lupus-erythematosus-similarities-and-differences-with-lupus-flare
#18
REVIEW
Ju-Yang Jung, Chang-Hee Suh
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, and its pathogenesis is unclear and complicated. Infection and SLE are similar in that they both cause inf lammatory reactions in the immune system; however, one functions to protect the body, whereas the other is activated to damage the body. Infection is known as one of the common trigger factors for SLE; there are a number of reports on infectious agents that provoke autoimmune response. Several viruses, bacteria, and protozoa were revealed to cause immune dysfunction by molecular mimicry, epitope spreading, and bystander activation...
May 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28483542/pathogenesis-of-cutaneous-lupus-erythema-associated-with-and-without-systemic-lupus-erythema
#19
REVIEW
Yu-Ping Zhang, Jian Wu, Yan-Fang Han, Zhen-Rui Shi, Liangchun Wang
Cutaneous lupus erythematosus(CLE) can be an individual disease only involving skin, or presents as part of the manifestations of SLE. A small proportion of CLE may progress into SLE, however, the underlying pathogenic mediators remain elusive. By only including researches that clearly described if the subtypes of CLE presented by enrolled subjects was associated with or without SLE, we provided an overview of antibodies, inflammatory cells and inflammatory molecular mediators identified in blood and skin that were possibly involved in lupus skin damages...
May 5, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28479222/effects-of-a-spleen-tyrosine-kinase-inhibitor-on-progression-of-the-lupus-nephritis-in-mice
#20
Maki Kitai, Noboru Fukuda, Takahiro Ueno, Morito Endo, Takashi Maruyama, Masanori Abe, Kazuyoshi Okada, Masayoshi Soma, Koichi Matsumoto
The Fc receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney...
March 25, 2017: Journal of Pharmacological Sciences
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