Abstract:
INTRODUCTION:Our objective was to examine the role of the janus-activated kinase (JAK) pathway in the modulation of tumor necrosis factor-α (TNF)-induced-IL-18 bioactivity by reduction of caspase-1 function. METHODS:Caspase-1 expression in rheumatoid arthritis (RA) synovial fibroblasts treated with TNF was assessed by qRT-PCR and Western blot. Interleukin (IL)-18 was assessed by enzyme-linked immunosorbent assay (ELISA) in cell lysates and conditioned media and detected by immunofluorescence (IF) staining in RA synovial fibroblasts. The critical pathways for TNF-induced caspase-1 expression were determined by using chemical inhibitors of signaling followed by TNF stimulation. IL-18 bioactivity was assessed using human myelomonocytic KG-1 cells. RESULTS:TNF induced RA synovial fibroblast caspase-1 expression at the protein level in a time-dependant manner (P < 0.05). Blocking the JAK pathway reduced TNF-induced-caspase-1 expression at the transcriptional and protein levels by approximately 60% and 40%, respectively (P < 0.05). Blocking the JAK pathway reduced TNF-induced-caspase-1 expression at the transcriptional, protein, and activity levels by approximately 60%, 40%, and 53%, respectively (P < 0.05). We then confirmed by IF that TNF-induced IL-18 and investigated roles of the ERK1/2 and JAK pathways. Blocking the JAK pathway, TNF induced intracytoplasmic granular IL-18 expression suggesting a defect of caspase-1. Finally, blocking the JAK pathway, we observed a reduction of IL-18 bioactivity by 52% in RA synovial fibroblasts (P < 0.05). CONCLUSIONS:These results provide a new way to regulate TNF-induced-IL-18 bioactivity by blocking capase-1. These data present a novel role for JAK inhibition in RA patients and emphasize JAK inhibition use as a new therapeutic option in RA management.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Marotte H,Tsou PS,Fedorova T,Pinney AJ,Lewis B,Koch AEdoi
10.1186/ar4551subject
Has Abstractpub_date
2014-04-24 00:00:00pages
R102issue
2eissn
1478-6354issn
1478-6362pii
ar4551journal_volume
16pub_type
杂志文章abstract::Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4230
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:The aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis. METHODS:Serum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy co...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0468-2
更新日期:2014-10-31 00:00:00
abstract:INTRODUCTION:HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characteri...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0881-1
更新日期:2015-12-16 00:00:00
abstract:INTRODUCTION:Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3123
更新日期:2010-01-01 00:00:00
abstract::This prospective study examined the association between physical activity and the incidence of self-reported stiff or painful joints (SPJ) among mid-age women and older women over a 3-year period. Data were collected from cohorts of mid-age (48-55 years at Time 1; n = 4,780) and older women (72-79 years at Time 1; n =...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2154
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:To understand the impact of yet undiagnosed non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) on work outcomes in a cohort of patients with long-lasting chronic low back pain (CLBP). METHODS:Data were used from a primary care CLBP cohort that was established to understand t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1333-x
更新日期:2017-06-17 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: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: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::Pulmonary involvement is a common complication of vasculitides, especially small vessel vasculitides. This review provides an overview of vasculitic manifestations of the lung as well as of other organs involved in vasculitides. Furthermore, it provides the diagnostic procedures required to asses a patient with vascul...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3307
更新日期:2011-06-30 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyperreactivity. The underlying causes of the diffuse B-cell over-reactivity are unclear, but potential candidates include (a) intrinsic hyper-reactivity leading to polyclonal B-cell activation wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3433
更新日期:2011-01-01 00:00:00
abstract::The transcription factor STAT-1 (signal transducer and activator of transcription-1) plays a pivotal role in the expression of inflammatory gene products involved in the pathogenesis of arthritis such as various cytokines and the CD40/CD40 ligand (CD40/CD40L) receptor-ligand dyad. The therapeutic efficacy of a synthet...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1869
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Anti-citrullinated protein antibody (ACPA) reactivities precede clinical onset of rheumatoid arthritis (RA), and it has been suggested that ACPA reactivities towards distinct target proteins may be associated with differences in RA phenotypes. We aimed to assess the prevalence of baseline ACPA reactivities i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-018-1635-7
更新日期:2018-07-13 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:BACKGROUND:Signs of inflammation in cerebrospinal fluid (CSF) of rheumatoid arthritis patients correlate positively with fatigue, a central nervous system (CNS)-related symptom that can be partially suppressed by TNF blockade. This suggests a possible role for CNS inflammation in arthritis that may be affected by TNF b...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-1846-6
更新日期:2019-02-15 00:00:00
abstract:BACKGROUND:The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. MET...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02313-w
更新日期:2020-09-29 00:00:00
abstract:INTRODUCTION:We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines ye...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3237
更新日期:2011-02-03 00:00:00
abstract:BACKGROUND:In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1147-2
更新日期:2016-10-22 00:00:00
abstract::With little in the way of effective therapeutic strategies to target the innate immune response, a better understanding of the critical pathways regulating neutrophil and macrophage responses in inflammation is key to the development of novel therapies. Hypoxia inducible factor (HIF) was originally identified as a cen...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2632
更新日期:2009-01-01 00:00:00
abstract::The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important function in human endothelial cell proliferation, and as such provides a valuable target in both inflammation and cancer. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased synovial vascularity, and henc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2340
更新日期:2007-01-01 00:00:00
abstract::Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13075-020-02156-5
更新日期:2020-03-24 00:00:00
abstract:INTRODUCTION:Rheumatic diseases are among the most common and debilitating health problems in the United States. These diseases are chronic, can result in severe decrements of physical and psychosocial functioning and affect patients' overall quality of life. A consensus regarding the best patient outcomes to be measur...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3219
更新日期:2011-01-05 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::Anti-Sa antibodies are detected in the serum of 20-47% of patients with rheumatoid arthritis. These antibodies have a high degree of specificity for the disease, and appear to identify a subset of early rheumatoid arthritis patients destined to have aggressive and destructive disease. It has recently been confirmed th...
journal_title:Arthritis research & therapy
pub_type: 评论,杂志文章,评审
doi:10.1186/ar1171
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1447-1
更新日期:2017-11-02 00:00:00
abstract:BACKGROUND:The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS:All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Sp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1776-8
更新日期:2018-12-19 00:00:00
abstract:BACKGROUND:The aim of this study was to develop a patient-reported questionnaire that is suitable to detect periodontitis (PD) in patients with rheumatoid arthritis (RA). METHODS:A self-reported questionnaire containing 12 items potentially relevant to PD and dentists' semiquantitative assessment of PD (no/mild/modera...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-019-1982-z
更新日期:2019-08-29 00:00:00
abstract::Prostaglandin E2 (PGE2) plays an important role in bone development and metabolism. To interfere therapeutically in the PGE2 pathway, however, knowledge about the involved enzymes (cyclooxygenases) and receptors (PGE2 receptors) is essential. We therefore examined the production of PGE2 in cultured growth plate chondr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1948
更新日期:2006-01-01 00:00:00
abstract::Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of com...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3204
更新日期:2011-02-01 00:00:00
abstract::TNF receptor-associated periodic syndrome (TRAPS) is a dominantly inherited disease caused by missense mutations in the TNF receptor 1 (TNFR1) gene. Patients suffer from periodic bouts of severe abdominal pain, localised inflammation, migratory rashes, and fever. More than 40 individual mutations have been identified,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2197
更新日期:2007-01-01 00:00:00