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lupus nephritis murine model

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https://www.readbyqxmd.com/read/29237779/estrogen-receptor-%C3%AE-signaling-exacerbates-immune-mediated-nephropathies-through-alteration-of-metabolic-activity
#1
Chelsea Corradetti, Neelakshi R Jog, Matteo Cesaroni, Michael Madaio, Roberto Caricchio
Glomerulonephritis is one of the most serious manifestations of systemic lupus erythematous (SLE). Because SLE is ≥10 times more common in women, a role for estrogens in disease pathogenesis has long been suspected. Estrogen receptor α (ERα) is highly expressed in renal tissue. We asked whether ERα expression contributes to the development of immune-mediated nephropathies like in lupus nephritis. We tested the overall effects of estrogen receptors on the immune response by immunization with OVA and induction of chronic graft-versus-host disease in female ERα-knockout mice...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29190833/lupus-nephritis-progression-in-fc%C3%AE-riib-yaa-mice-is-associated-with-early-development-of-glomerular-electron-dense-deposits-and-loss-of-renal-dnase-i-in-severe-disease
#2
Kjersti Daae Horvei, Hege Lynum Pedersen, Silje Fismen, Dhivya Thiyagarajan, Andrea Schneider, Ole Petter Rekvig, Thomas H Winkler, Natalya Seredkina
FcγRIIB-/-yaa mice develop severe lupus glomerulonephritis due to lack of an inhibitory immune cell receptor combined with a Y-chromosome linked autoimmune accelerator mutation. In the present study, we have investigated nephritis development and progression in FcγRIIB-/-yaa mice to find shared features with NZB/NZW F1 lupus prone mice and human disease. We sacrificed 25 male FcγRIIB-/-yaa mice at various disease stages, and grouped them according to activity and chronicity indices for lupus nephritis. Glomerular morphology and localization of electron dense deposits containing IgG were further determined by immune electron microscopy...
2017: PloS One
https://www.readbyqxmd.com/read/29186654/treatment-with-allogenic-mesenchymal-stromal-cells-in-a-murine-model-of-systemic-lupus-erythematosus
#3
Chiara Tani, Sabrina Vagnani, Linda Carli, Francesca Querci, Anja A Kühl, Simone Spieckermann, Constanze Pamela Cieluch, Simone Pacini, Rita Fazzi, Marta Mosca
Objective: Pre-clinical and uncontrolled studies in patients with systemic lupus erythematosus (SLE) showed that mesenchymal stromal cells (MSCs) have a potential therapeutic role in refractory cases. The optimal therapeutic strategy in these patients remain to be elucidated. Our aim was to test the hypothesis that repeated administrations of 1×106/kg body weight of allogenic MSCs, that is a significantly lower dosage with respect to the fixed 1×106 MSC used in animal models, can be effective in improving the clinical course of a murine SLE model...
November 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29069649/the-systemic-activation-of-programmed-death-1-pd-l1-axis-protects-systemic-lupus-erythematosus-model-from-nephritis
#4
Wenjun Liao, Hua Zheng, Sha Wu, Yanmei Zhang, Wei Wang, Zili Zhang, Chenfei Zhou, Hongjun Wu, Jie Min
BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. METHODS: The murine PD-L1-Ig was injected into SLE-prone mice...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28950886/hm71224-a-selective-bruton-s-tyrosine-kinase-inhibitor-attenuates-the-development-of-murine-lupus
#5
Yu-Yon Kim, Ki Tae Park, Sun Young Jang, Kyu Hang Lee, Joo-Yun Byun, Kwee Hyun Suh, Young-Mi Lee, Young Hoon Kim, Kwang Woo Hwang
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with B cell hyperactivity, and lupus nephritis (LN), in particular, is promoted by the production of autoantibodies and immune complex deposition. Bruton's tyrosine kinase (BTK) plays critical roles in B cell receptor-related and Fc receptor-related signaling. We aimed to investigate the impact of therapeutic intervention with HM71224 (LY3337641), a selective BTK inhibitor, on the development of murine SLE-like disease features...
September 26, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28880016/-5r-5-hydroxytriptolide-ameliorates-anti-glomerular-basement-membrane-glomerulonephritis-in-nzw-mice-by-regulating-fc%C3%AE-receptor-signaling
#6
Qing Qi, Heng Li, Ze-Min Lin, Xiao-Qian Yang, Feng-Hua Zhu, Yu-Ting Liu, Mei-Juan Shao, Lu-Yao Zhang, Yan-Sheng Xu, Yu-Xi Yan, Lan-Lan Sun, Shi-Jun He, Wei Tang, Jian-Ping Zuo
(5R)-5-hydroxytriptolide (LLDT-8) is a novel triptolide analog that has been identified as a promising candidate for treating autoimmune diseases and has been shown to be effective in treating murine collagen-induced arthritis and lupus nephritis. In the present study, we investigated the therapeutic effect and possible mechanism of action of LLDT-8 in a murine anti-glomerular basement membrane (GBM) glomerulonephritis model. NZW mice were injected with rabbit anti-GBM serum (500 μL, ip). The mice were orally treated with LLDT-8 (0...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28747139/a-monoclonal-antibody-against-cd86-and-its-protection-in-a-murine-lupus-nephritis-model-of-chronic-graft-versus-host-disease
#7
Lianhua Han, Lijun Shen, Ying Zhu, Yuhua Qiu
CONTEXT: Lupus nephritis is the most common complication that causes the death of systemic lupus erythematosus patients. CD28/CTLA4 and their ligands CD80 or CD86 costimulatory pathway play a pivotal role in autoimmune disease and organ transplantation. OBJECTIVES: We generated a monoclonal antibody (clone 1D1) against human CD86 (1D1) that could recognize both human and mouse CD86, and blocked the CD86/CD28 costimulatory pathway with our mAb on a murine lupus nephritis model induced with chronic graft-versus-host disease (cGVHD)...
July 26, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28722110/renal-infiltrating-cd11c-cells-are-pathogenic-in-murine-lupus-nephritis-through-promoting-cd4-t-cell-responses
#8
X Liao, J Ren, A Reihl, T Pirapakaran, B Sreekumar, T E Cecere, C M Reilly, X M Luo
Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE), causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c(+) myeloid cell population in LN...
November 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#9
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#10
Laetitia Laurent, Awena Le Fur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
August 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28626343/anti-osm-antibody-inhibits-tubulointerstitial-lesion-in-a-murine-model-of-lupus-nephritis
#11
Qingjuan Liu, Yunxia Du, Kejun Li, Wei Zhang, Xiaojuan Feng, Jun Hao, Hongbo Li, Shuxia Liu
The purpose of this study was to investigate the role of oncostatin M (OSM) in tubulointerstitial lesion (TIL) in lupus nephritis (LN). We found that OSM was highly expressed in the renal tissue of LN mice. OSM is one of the interleukin-6 cytokine family members. In order to clarify the role and mechanism of OSM in LN, mice with LN were treated with anti-OSM antibody or isotype antibody. We evaluated the tubular epithelial-mesenchymal transdifferentiation (EMT) by detecting the E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin (FN) expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28515361/lupus-and-proliferative-nephritis-are-pad4-independent-in-murine-models
#12
Rachael A Gordon, Jan M Herter, Florencia Rosetti, Allison M Campbell, Hiroshi Nishi, Michael Kashgarian, Sheldon I Bastacky, Anthony Marinov, Kevin M Nickerson, Tanya N Mayadas, Mark J Shlomchik
Though recent reports suggest that neutrophil extracellular traps (NETs) are a source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we recently showed that inhibition of NETs by targeting the NADPH oxidase complex via cytochrome b-245, β polypeptide (cybb) deletion exacerbated disease in the MRL.Faslpr lupus mouse model. While these data challenge the paradigm that NETs promote lupus, it is conceivable that global regulatory properties of cybb and cybb-independent NETs confound these findings...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28242713/activation-of-peroxisome-proliferator-activator-receptor-%C3%AE-%C3%AE-improves-endothelial-dysfunction-and-protects-kidney-in-murine-lupus
#13
Miguel Romero, Marta Toral, Iñaki Robles-Vera, Manuel Sánchez, Rosario Jiménez, Francisco O'Valle, Alba Rodriguez-Nogales, Francisco Pérez-Vizcaino, Julio Gálvez, Juan Duarte
Women with systemic lupus erythematosus exhibit a high prevalence of hypertension, endothelial dysfunction, and renal injury. We tested whether GW0742, a peroxisome proliferator activator receptor β/δ (PPARβ/δ) agonist, ameliorates disease activity and cardiovascular complications in a female mouse model of lupus. Thirty-week-old NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with GW0742 or with the PPARβ/δ antagonist GSK0660 plus GW0742 for 5 weeks. Blood pressure, plasma double-stranded DNA autoantibodies and cytokines, nephritis, hepatic opsonins, spleen lymphocyte populations, endothelial function, and vascular oxidative stress were compared in treated and untreated mice...
April 2017: Hypertension
https://www.readbyqxmd.com/read/28130617/prolactin-has-a-pathogenic-role-in-systemic-lupus-erythematosus
#14
Luis J Jara, Gabriela Medina, Miguel A Saavedra, Olga Vera-Lastra, Honorio Torres-Aguilar, Carmen Navarro, Monica Vazquez Del Mercado, Luis R Espinoza
Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction...
April 2017: Immunologic Research
https://www.readbyqxmd.com/read/28039299/hyperactivation-of-the-nlrp3-inflammasome-in-myeloid-cells-leads-to-severe-organ-damage-in-experimental-lupus
#15
Ailing Lu, Hua Li, Junling Niu, Shuxian Wu, Guang Xue, Xiaomin Yao, Qiuhong Guo, Nianhong Wan, Paride Abliz, Guiwen Yang, Liguo An, Guangxun Meng
Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27992697/vista-deficiency-accelerates-the-development-of-fatal-murine-lupus-nephritis
#16
Sabrina Ceeraz, Petra A Sergent, Sean F Plummer, Alan R Schned, Dov Pechenick, Christopher M Burns, Randolph J Noelle
OBJECTIVE: The targeting of negative checkpoint regulators as a means of augmenting antitumor immune responses is now an increasingly used and remarkably effective approach to the treatment of several human malignancies. The negative checkpoint regulator VISTA (V-domain Ig-containing suppressor of T cell activation; also known as programmed death 1 homolog or as death domain 1α) suppresses T cell responses and regulates myeloid activities. We proposed that exploitation of the VISTA pathway is a novel strategy for the treatment of human autoimmune disease, and therefore we undertook this study to determine the impact of VISTA genetic deficiency on lupus development in a lupus-prone mouse strain...
April 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27927780/genomic-analysis-of-kidney-allograft-injury-identifies-hematopoietic-cell-kinase-as-a-key-driver-of-renal-fibrosis
#17
Chengguo Wei, Li Li, Madhav C Menon, Weijia Zhang, Jia Fu, Brian Kidd, Karen L Keung, Christopher Woytovich, Ilana Greene, Wenzhen Xiao, Fadi Salem, Zhengzi Yi, John Cijiang He, Joel T Dudley, Barbara Murphy
Renal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase (Hck), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration-approved drug, potently binds Hck with high selectivity...
May 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27924862/mesenchymal-stem-cell-transplantation-can-restore-lupus-disease-associated-mirna-expression-and-th1-th2-ratios-in-a-murine-model-of-sle
#18
Eun Wha Choi, MinJae Lee, Ji Woo Song, Il Seob Shin, Sung Joo Kim
C3.MRL-Fas(lpr)/J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis, and severe lymphoproliferation symptoms. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and cyclophosphamide treatment in C3.MRL-Fas(lpr)/J mice using a murine SLE model. C3.MRL-Fas(lpr)/J mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Background-matched control C3H mice treated with saline (N) were also compared...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27811014/regulated-necrosis-related-molecule-mrna-expression-in-humans-and-mice-and-in-murine-acute-tissue-injury-and-systemic-autoimmunity-leading-to-progressive-organ-damage-and-progressive-fibrosis
#19
Mohsen Honarpisheh, Jyaysi Desai, Julian A Marschner, Marc Weidenbusch, Maciej Lech, Volker Vielhauer, Hans-Joachim Anders, Shrikant R Mulay
The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs...
December 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27786399/roles-of-tumour-necrosis-factor-related-weak-inducer-of-apoptosis-fibroblast-growth-factor-inducible-14-pathway-in-lupus-nephritis
#20
REVIEW
Jingyun Chen, Linlin Wei, Yumin Xia
As one of the manifestations of patients with systemic lupus erythematosus, lupus nephritis (LN) has high morbidity and mortality. Although the explicit mechanism of LN remains to be fully elucidated, there is increasing evidence to support the notion that tumour necrosis factor-related weak inducer of apoptosis (TWEAK), acting via its sole receptor, fibroblast growth factor-inducible 14 (Fn14), plays a pivotal role in such pathologic process. TWEAK/Fn14 interactions occur prominently in kidneys of LN, inducing inflammatory responses, angiogenesis, mesangial proliferation, filtration barrier injuries, renal fibrosis, etc...
February 2017: Nephrology
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