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lupus nephritis murine model

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
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...
January 28, 2017: Immunologic Research
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...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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...
December 7, 2016: Journal of the American Society of Nephrology: JASN
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
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
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
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
March 2017: Immunobiology
Chelsea Corradetti, Neelakshi R Jog, Stefania Gallucci, Michael Madaio, Siddharth Balachandran, Roberto Caricchio
Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates...
2016: PloS One
Samantha A Chalmers, Jing Wen, Justine Shum, Jessica Doerner, Leal Herlitz, Chaim Putterman
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that can affect multiple end organs. Kidney and brain are two of the organs most commonly involved in SLE. Past studies have suggested the importance of macrophages in the pathogenesis of lupus nephritis (LN). Furthermore, as the immune effectors of the brain, microglia have been implicated in pathways leading to neuropsychiatric SLE (NPSLE). We depleted macrophages and microglia using GW2580, a small colony stimulating factor-1 receptor (CSF-1R) kinase inhibitor, in MRL-lpr/lpr (MRL/lpr) mice, a classic murine lupus model that displays features of both LN and NPSLE...
August 26, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Fumi Miyagawa, Yutaka Tagaya, Keiko Ozato, Hideo Asada
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the production of autoantibodies against nuclear components. Recent genetic studies of SLE patients have revealed that IFN regulatory factor (IRF) 7 gene polymorphisms are associated with an increased risk of SLE, but the precise role of IRF7 in SLE development is not fully understood. We investigated the role of IRF7 in the pathogenesis of SLE using a mouse model and saw a curious dissociation of autoantibody production and development of glomerulonephritis...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Hui Wang, Jason S Knight, Jeffrey B Hodgin, Jintao Wang, Chiao Guo, Kyle Kleiman, Daniel T Eitzman
Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1(-/-)) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls...
2016: Scientific Reports
Rubina Novelli, Elena Gagliardini, Barbara Ruggiero, Ariela Benigni, Giuseppe Remuzzi
BACKGROUND/AIMS: Lupus nephritis (LN) is a frequent complication and a major predictor of poor prognosis of systemic lupus erythematosus. Immune complex deposition and T cell infiltration are crucial events in LN pathogenesis. B7-1 (CD80), normally expressed by antigen-presenting cells, is one of the major co-stimulators of T-cell activation through the binding with its counter-receptors CD28 and cytotoxic T-lymphocyte antigen-4. Unexpectedly, B7-1 induction was described at the podocyte level in patients affected by different renal diseases, including LN...
2016: Nephron
Yuko Matsuki-Muramoto, Kazuhisa Nozawa, Kaori Uomori, Iwao Sekigawa, Yoshinari Takasaki
OBJECTIVE: To clarify the mechanisms underlying lupus nephritis (LN) amelioration following bortezomib treatment. METHODS: Bortezomib was administered subcutaneously every 3 days to NZB/W F1 mice, and the serum anti-double stranded (ds) deoxyribonucleic acid (DNA) antibody titers and proteinuria levels were measured. The renal samples and the splenocytes were examined histologically or used for real-time quantitative reverse transcription-polymerase chain reaction analysis after 18 weeks of treatment...
January 2017: Modern Rheumatology
Kichul Ko, Jianing Wang, Stuart Perper, Yulei Jiang, Denisse Yanez, Natalya Kaverina, Junting Ai, Vladimir M Liarski, Anthony Chang, Yahui Peng, Li Lan, Susan Westmoreland, Lisa Olson, Maryellen L Giger, Li Chun Wang, Marcus R Clark
OBJECTIVE: In lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII. METHODS: This study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets...
November 2016: Arthritis & Rheumatology
Xiao Han, Yan Wang, Xiaoyan Zhang, Yuting Qin, Bo Qu, Lingling Wu, Jianyang Ma, Zhenyuan Zhou, Jie Qian, Min Dai, Yuanjia Tang, Edward K L Chan, John B Harley, Shiyu Zhou, Nan Shen
OBJECTIVE: Type I interferon (IFN) is a critical pathogenic factor during the progression of lupus nephritis (LN). Although microRNAs (miRNAs) have been shown to control the IFN response in immune cells in LN, the role of miRNAs in resident renal cells remains unclear. We undertook this study to investigate the role of microRNA-130b (miR-130b) in the IFN pathway in renal cells as well as its therapeutic effect in LN. METHODS: Kidney tissues from patients and (NZB × NZW)F1 lupus-prone mice were collected for detecting miR-130b levels...
September 2016: Arthritis & Rheumatology
A Wiener, A Schippers, N Wagner, F Tacke, T Ostendorf, N Honke, K Tenbrock, K Ohl
The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double-negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys...
July 2016: Clinical and Experimental Immunology
Wei Li, Hu Li, Mu Zhang, Mengqi Wang, Youxiu Zhong, Hezhen Wu, Yanfang Yang, Laurence Morel, Qun Wei
Systemic lupus erythematosus (SLE) is a serious disorder of immune regulation characterized by overproduction of autoantibodies, lupus nephritis, CD4+ T cell aberrant activation, and immune complex-mediated inflammation. The chronic graft vs. host disease (cGVHD) mouse model is a well-established model of SLE. Quercitrin is a natural compound found in Tartary buckwheat with a potential anti-inflammatory effect that is used to treat heart and vascular conditions. In our previous study, we determined that quercitrin is an immunosuppressant with beneficial effects in mouse models of immune diseases...
July 1, 2016: American Journal of Physiology. Renal Physiology
Andrew T Bender, Albertina Pereira, Kai Fu, Eileen Samy, Yin Wu, Lesley Liu-Bujalski, Richard Caldwell, Yi-Ying Chen, Hui Tian, Federica Morandi, Jared Head, Ursula Koehler, Melinda Genest, Shinji L Okitsu, Daigen Xu, Roland Grenningloh
Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors...
March 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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