Abstract:
:Glucocorticoids have successfully been used in the treatment of rheumatoid arthritis. Data suggest that 7alpha-hydroxy-dehydroepiandrosterone (7alpha-OH-DHEA), an immunostimulating metabolite of dehydroepiandrosterone, can block glucocorticoid-induced immune suppression. Formation of 7alpha-OH-DHEA is catalyzed by activity of cytochrome p450 enzyme 7b (Cyp7b). Recently, we reported that tumour necrosis factor (TNF)-alpha, IL-1alpha, IL-1beta and IL-17 enhance Cyp7b mRNA expression and induce a concomitant increase in the formation of 7alpha-OH-DHEA by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis patients. The aim of this study was to elucidate which signal transduction pathway is involved in the TNF-alpha-mediated induction of Cyp7b activity in FLS. We studied the effects of inhibitors of different signal transduction pathways on Cyp7b activity in FLS by measuring Cyp7b mRNA expression using reverse transcription PCR and by measuring the formation of 7alpha-OH-DHEA. We applied SN50, an inhibitor of nuclear translocation of transcription factors (i.e. activator protein-1 [AP-1] and nuclear factor-kappaB [NF-kappaB]); PSI, a proteasome inhibitor that prevents IkappaB degradation and thereby NF-kappaB release; SP600125, a c-Jun N-terminal kinase (JNK) inhibitor; and the mitogen-activated protein kinase inhibitors PD98059 (extracellular signal-regulated kinase) and SB203580 (p38). Cyp7b is constitutively expressed in RA FLS and can be activated in response to TNF-alpha. SN50 and PSI prevented the TNF-alpha-induced increase in Cyp7b activity, whereas the mitogen-activated protein kinase inhibitors PD98059 and SB203580 had no effect. In addition, inhibition of Cyp7b mRNA expression and activity was observed with SN50, PSI and SP600125, suggesting that NF-kappaB and AP-1 induce Cyp7b transcription. These findings suggest that NF-kappaB and AP-1 are involved in the TNF-alpha-enhanced formation of the dehydroepiandrosterone metabolite 7alpha-OH-DHEA. Our results are in accordance with presence of AP-1 and NF-kappaB binding sites in the Cyp7b promoter.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Dulos J,Kaptein A,Kavelaars A,Heijnen C,Boots Adoi
10.1186/ar1819keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
R1271-80issue
6eissn
1478-6354issn
1478-6362pii
ar1819journal_volume
7pub_type
杂志文章abstract:INTRODUCTION:Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have be...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/s13075-014-0507-z
更新日期:2014-12-14 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02269-x
更新日期:2020-07-25 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:The objective was to study immune regulation in a mouse model of rheumatoid arthritis that exhibits considerable heterogeneity of disease activity. METHODS:T-cell receptor transgenic mice, in which nearly all CD4+ T cells recognize a single peptide of type II collagen, were immunized with collagen and obs...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2795
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:The objective of this study was to assess natural microbial agents, history and risk factors for total joint arthroplasty (TJA) infections in patients receiving tumor necrosis factor (TNF)α-blockers, through the French RATIO registry and a case-control study. METHODS:Cases were TJA infections during TNFα-...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3087
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4368
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVES:To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified. METHODS:We recruited patients with at least 1 SARD ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1929-4
更新日期:2019-06-14 00:00:00
abstract::Behçet's disease is characterized by recurrent aphthous stomatitis, uveitis, genital ulcers, and skin lesions. The role of the HLA-B*51 gene has been confirmed in recent years, although its contribution to the overall genetic susceptibility to Behçet's disease was estimated to be only 19%. The production of a variety ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar757
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Pateclizumab (MLTA3698A) is a humanized mAb against lymphotoxin α (LTα), a transiently expressed cytokine on activated B and T cells (Th1, Th17), which are implicated in rheumatoid arthritis (RA) pathogenesis. This study was conducted to assess the safety, tolerability, < NOTE: For clarity and per AMA/S-W ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar3554
更新日期:2012-01-08 00:00:00
abstract:INTRODUCTION:Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselecte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0756-5
更新日期:2015-08-28 00:00:00
abstract::Collagen-induced arthritis (CIA) is a chronic inflammatory disease bearing all the hallmarks of rheumatoid arthritis, e.g. polyarthritis, synovitis, and subsequent cartilage/bone erosions. One feature of the disease contributing to joint damage is synovial hyperplasia. The factors responsible for the hyperplasia are u...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1205
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:The arthritis-specific Work Productivity Survey (WPS) was developed to evaluate productivity limitations associated with arthritis within and outside the home. There is an unmet need for an instrument assessing similar productivity limitations in axial spondyloarthritis (axSpA), including nonradiographic a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4680
更新日期:2014-08-06 00:00:00
abstract::miRNAs have been shown to play essential regulatory roles in the innate immune system. They function at multiple levels to shape the innate immune response and maintain homeostasis by direct suppression of the expression of their target proteins, preferentially crucial signaling components and transcription factors. S...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4194
更新日期:2013-04-09 00:00:00
abstract:INTRODUCTION:Dual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout. METHODS:Seventy-three patients wi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4343
更新日期:2013-10-23 00:00:00
abstract::Systematic lupus erythematosus (SLE) is a complex disease for which molecular diagnostics are limited and pathogenesis is not clearly understood. Important information is provided in this regard by identification and characterization of more specific molecular and cellular targets in SLE immune cells and target tissue...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3701
更新日期:2012-02-20 00:00:00
abstract:INTRODUCTION:Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) share genetic and clinical features. IBD is associated with the presence of antibodies to a variety of commensal microorganisms including anti-Saccharomyces cerevesiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), anti-I2 (...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4350
更新日期:2013-10-26 00:00:00
abstract:BACKGROUND:To aim was to investigate the additional value of incorporating the de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS) spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS. METHOD:Baseline and 4-year radiographs from 98 consecutive patients from the Gronin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1285-1
更新日期:2017-04-26 00:00:00
abstract:INTRODUCTION:Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3476
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skel...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13075-018-1786-6
更新日期:2018-12-27 00:00:00
abstract:INTRODUCTION:miR-146a is one of the first identified miRNAs expressed differentially in osteoarthritis (OA) cartilage. However, the role it plays in OA pathogenesis is not clear. The aim of this study is to identify a molecular target of miR-146a, thereby elucidating its function in chondrocytes during OA pathogenesis....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3798
更新日期:2012-04-16 00:00:00
abstract:INTRODUCTION:Autoantibodies against mutated and citrullinated vimentin (MCV) represent a novel diagnostic marker for rheumatoid arthritis (RA). Recently, an increased sensitivity for anti-MCV compared to autoantibodies against cyclic citrullinated peptides (anti-CCP2) was shown in cohorts of patients with early RA and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3057
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-016-1137-4
更新日期:2016-11-08 00:00:00
abstract:BACKGROUND:Biologic disease-modifying antirheumatic drugs (bDMARDs) are important options for managing rheumatoid arthritis (RA). Once patients achieve disease control, clinicians may consider dose reduction or withdrawal of the bDMARD. Results from published studies indicate that some patients will maintain remission;...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1937-4
更新日期:2019-07-05 00:00:00
abstract:BACKGROUND:The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02351-4
更新日期:2020-10-19 00:00:00
abstract:BACKGROUND:Interstitial lung disease (ILD) is the principal cause of death in polymyositis/dermatomyositis (PM/DM). Here we investigated prognostic factors for death and serious infection in PM/DM-ILD using the multicenter database. METHODS:We retrospectively reviewed baseline demographic, clinical and laboratory find...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1506-7
更新日期:2018-01-11 00:00:00
abstract:INTRODUCTION:The goals of this study were to examine the oxemic regulation of Wnt signaling to explore whether Wnt signaling accelerates the age-related degeneration of nucleus pulposus cells, and if so, to define the mechanism underlying this effect. We investigated the expression of Klotho, a newly identified antiagi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3830
更新日期:2012-05-02 00:00:00
abstract:INTRODUCTION:Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representat...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2519
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:To assess the associations between aspartate transaminase/alanine transaminase ratio (DRR) and mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). PATIENTS AND METHODS:This was a retrospective cohort study, which included 522 patients with PM/DM-ILD whose...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02286-w
更新日期:2020-09-20 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies and immune complex deposition in various organs. Aberrations in the T lymphocyte compartment and dysregulated cytokine production are key features of SLE pathogenesis and disease progression. Recently...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3194
更新日期:2010-01-01 00:00:00
abstract::Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-termina...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1193
更新日期:2004-01-01 00:00:00