Abstract:
BACKGROUND:The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB x NZW) F1 murine lupus model. METHODS:Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg oral spironolactone or vehicle. Proteinuria, renal function, and serum autoantibody levels were monitored. Renal histopathology, immune complex deposition, and immunohistochemistry were analyzed at various time points. Targeted microarray analysis was performed on renal tissue, with subsequent real-time PCR analysis of several differentially expressed genes. RESULTS:Treatment with spironolactone was well tolerated by the mice throughout the course of their disease progression, with no significant differences in azotemia or serum potassium levels between vehicle-treated and spironolactone-treated animals. By 36 weeks of age, fewer spironolactone-treated mice developed nephrotic range proteinuria as compared with the control mice (control 70.8%, 25 mg/kg spironolactone 51.3%, and 50 mg/kg spironolactone 48.6%). Compared with control mice, mice treated with 25 mg/kg spironolactone had significantly lower serum anti-single-stranded DNA levels (2,042 microg/ml versus 1,036 microg/ml; P = 0.03) and anti-double-stranded DNA levels (3,433 microg/ml versus 614 microg/ml; P = 0.05). Spironolactone-treated mice exhibited decreased histopathologic evidence of inflammation and tissue damage, as compared with control mice. Additionally, spironolactone treatment resulted in decreased expression in the kidney of several inflammatory and proapoptotic genes, including those encoding interferon-gamma, B lymphocyte stimulator (BlyS), tumor necrosis factor related apoptosis inducing ligand (TRAIL), tumor necrosis factor related weak inducer of apoptosis (TWEAK), and Fas ligand. CONCLUSION:Aldosterone receptor blockade is safe and well tolerated in progressive murine lupus nephritis, and it results in decreased levels of clinical proteinuria, lower serum levels of autoantibodies, and decreased kidney damage. It appears to modulate inflammatory changes during the progression of glomerulonephritis and may also have a previously undescribed role in attenuating apoptosis.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Monrad SU,Killen PD,Anderson MR,Bradke A,Kaplan MJdoi
10.1186/ar2353subject
Has Abstractpub_date
2008-01-01 00:00:00pages
R5issue
1eissn
1478-6354issn
1478-6362pii
ar2353journal_volume
10pub_type
杂志文章abstract:INTRODUCTION:BRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known to be implicated in the production of pro-inflammatory cytokines.We have observed that sera from rheumatoid arthritis (RA) patients recogniz...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3165
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Validated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canad...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2091-8
更新日期:2020-01-15 00:00:00
abstract:INTRODUCTION:A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2817
更新日期:2009-01-01 00:00:00
abstract::B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2780
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The aim of this study was to understand whether acupuncture can decrease the risk of coronary heart disease (CHD) in patients with fibromyalgia. METHODS:Using data from the Taiwanese National Health Insurance Research Database, we performed a propensity score-matched cohort study to analyze patients with fi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1239-7
更新日期:2017-02-28 00:00:00
abstract:INTRODUCTION:The revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3479
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accurac...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4383
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS. METHODS:The Cochrane Library, EMBASE, MEDLINE, PsychInfo and SPORTDISCUS (through April 2009) and the re...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar3002
更新日期:2010-01-01 00:00:00
abstract::Following publication of the original article [1], the authors reported a typesetting error. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1753-2
更新日期:2018-11-05 00:00:00
abstract::Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3657
更新日期:2012-01-30 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemoki...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3778
更新日期:2012-03-14 00:00:00
abstract::Inflammation and inflammatory responses are modulated by a bidirectional communication between the neuroendocrine and immune system. Many lines of research have established the numerous routes by which the immune system and the central nervous system (CNS) communicate. The CNS signals the immune system through hormona...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1002
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse. METHODS:The prooxidative, antiproliferative, and cytotoxic effects...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4351
更新日期:2013-10-28 00:00:00
abstract:INTRODUCTION:Tumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatmen...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar3054
更新日期:2010-01-01 00:00:00
abstract::In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1737
更新日期:2005-01-01 00:00:00
abstract::Susceptibility for giant cell arteritis increases with chronological age, in parallel with age-related restructuring of the immune system and age-induced remodeling of the vascular wall. Immunosenescence results in shrinkage of the naïve T-cell pool, contraction of T-cell diversity, and impairment of innate immunity. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3358
更新日期:2011-08-02 00:00:00
abstract::Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction distur...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1848
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful. Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common. Endocannabinoids have the...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0437-9
更新日期:2014-09-27 00:00:00
abstract::There is increasing recognition that central pain sensitivity plays an important role in pain severity among patients with osteoarthritis. Murphy and colleagues identified clusters of patients with osteoarthritis according to pain severity and accompanying symptoms, and one of these groups appeared to have a greater d...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3499
更新日期:2011-01-01 00:00:00
abstract::Autoantibodies targeting intracellular proteins involved in key processes are detected in patients with idiopathic inflammatory myopathies. These myositis-specific autoantibodies have been increasingly demonstrated to correlate with distinct clinical phenotypes within the myositis spectrum. This review highlights the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3275
更新日期:2011-03-18 00:00:00
abstract:INTRODUCTION:Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultra...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3742
更新日期:2012-02-15 00:00:00
abstract:INTRODUCTION:This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort. METHODS:The magnitude of association for each genotype was assessed in 1,046 RA subjects...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2969
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The decreased disc height characteristic of intervertebral disc (IVD) degeneration has often been linked to low back pain, and thus regeneration strategies aimed at restoring the disc extracellular matrix and ultimately disc height have been proposed as potential treatments for IVD degeneration. One such t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2611
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruct...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4474
更新日期:2014-02-05 00:00:00
abstract::Bone morphogenetic proteins (BMPs) are expressed during osteogenesis and their action is regulated by corresponding BMP inhibitors. Chordin (a well recognized BMP inhibitor) and BMP-2 are expressed during osteogenic differentiation of human mesenchymal stem cells. Chordin inhibition induces human mesenchymal stem cell...
journal_title:Arthritis research & therapy
pub_type: 社论
doi:10.1186/ar2467
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:During pregnancy, many patients with rheumatoid arthritis (RA) experience disease improvement, whereas patients with ankylosing spondylitis often suffer from persistent active disease. Here we investigated whether pregnancy-related changes in disease activity were associated with changes in the proportion an...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0925-1
更新日期:2016-01-22 00:00:00
abstract:INTRODUCTION:The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4442
更新日期:2014-01-17 00:00:00
abstract:INTRODUCTION:In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown. METHODS:Incidence and progression of CAC were compared in 155 patie...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4314
更新日期:2013-09-25 00:00:00
abstract::The development of spontaneous autoimmunity in inbred strains of rodents has allowed us to investigate the molecular basis of chronic inflammatory disease in ways that would not be possible in humans. Recently, two new mouse models of autoimmune inflammatory polyarthritis have been reported that demonstrate how altera...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1185
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3827
更新日期:2012-05-01 00:00:00