Abstract:
:Sphingolipids are components of the plasma membrane whose metabolic manipulation is of interest as a potential therapeutic approach in a number of diseases. Sphingosine kinase 1 (SphK1), the major kinase that phosphorylates sphingosine to sphingosine-1-phosphate (S1P), was previously shown by our group and others to modulate inflammation in murine models of inflammatory arthritis, inflammatory bowel disease and asthma. Sphingosine kinase 2's (SphK2) impact on inflammation is less well known, as variable results were reported depending on the disease model. A specific SphK2 inhibitor inhibited inflammatory arthritis in one model, while siRNA knockdown of SphK2 worsened arthritis in another. We previously demonstrated that SphK1 deficient mice are protected against development of hTNF-α-induced arthritis. To investigate the role of SphK2 in TNF-α-induced arthritis, we developed SphK2 deficient hTNF-α overexpressing mice and separately treated hTNF-α mice with ABC294640, a SphK2-specific inhibitor. Our data show that genetic inhibition of SphK2 did not significantly impact the severity or progression of inflammatory arthritis, while pharmacologic inhibition of SphK2 led to significantly more severe arthritis. Compared to vehicle-treated mice, ABC294640 treated mice also had less S1P in whole blood and inflamed joint tissue, although the differences were not significant. ABC294640 treatment did not affect SphK1 activity in the inflamed joint while little SphK2 activity was detected in the joint. We conclude that the differences in the inflammatory phenotype in genetic inhibition versus pharmacologic inhibition of SphK2 can be attributed to the amount of ABC294640 used in the experiments versus the impact of acute inhibition of SphK2 with ABC294640 versus genetically induced life-long SphK2 deficiency. Thus, inhibition of SphK2 appears to be proinflammatory in contrast to the clear anti-inflammatory effects of blocking SphK1. Therapies directed at this sphingosine kinase pathways will need to be specific in their targeting of sphingosine kinases.
journal_name
Rheumatol Intjournal_title
Rheumatology internationalauthors
Baker DA,Eudaly J,Smith CD,Obeid LM,Gilkeson GSdoi
10.1007/s00296-012-2493-2subject
Has Abstractpub_date
2013-10-01 00:00:00pages
2677-81issue
10eissn
0172-8172issn
1437-160Xjournal_volume
33pub_type
杂志文章abstract::We have recently reported on two cases of scleroderma patients with ANCA-associated vasculitis for the first time in Korea. In order to explore the nature of this disease combination, we pooled together all the previously known cases and statistically analyzed them. Out of the 50 selected cases, survival analysis was ...
journal_title:Rheumatology international
pub_type: 杂志文章,评审
doi:10.1007/s00296-005-0011-5
更新日期:2006-03-01 00:00:00
abstract::The aim was to study the association of smoking with the activity and severity of systemic lupus erythematosus (SLE) and the production of antibodies to dsDNA. The study included 223 SLE patients attending the outpatient clinics at Helsinki University Central Hospital. The history of smoking was obtained by personal i...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-013-2889-7
更新日期:2014-03-01 00:00:00
abstract::Intraperitoneal injection of pristane induced a clinical peripheral arthritis and/or tenosynovitis in 40% of 40 Balb/cJ/Ola mice. Hind paws were always affected first and fore paws were frequently involved. Involvement of knee joints was only apparent histologically. Some clinically unaffected animals and apparently u...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/BF00541361
更新日期:1984-01-01 00:00:00
abstract::We investigated the effect of chrysotherapy on the Fc and complement receptor binding activity of peripheral blood (PB) monocytes and peritoneal (PE) macrophages isolated from normal rats and rats with adjuvant induced arthritis. The adjuvant induced severe disease in Dark Agouti (DA) rats and less marked disease in J...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/BF00270454
更新日期:1988-01-01 00:00:00
abstract::Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a p...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-008-0540-9
更新日期:2008-07-01 00:00:00
abstract::The current clinical and laboratory parameters of Takayasu arteritis (TA) are insufficient for proper assessment of disease activity. The aims of this study were to investigate the markers of endothelial injury and repair, including circulating endothelial cell (CEC), circulating endothelial progenitor cell (CEPC) and...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-013-2937-3
更新日期:2014-08-01 00:00:00
abstract::Systemic sclerosis (SSc) is a generalized disorder characterized by fibrosis and vascular obliteration in the skin, lung, gastrointestinal tract, and kidney. One of its two subsets is a stable, limited cutaneous group (lSSc). Pulmonary involvement in scleroderma is common, and several types of pulmonary disorders are ...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-002-0230-y
更新日期:2002-09-01 00:00:00
abstract::The association of familial Mediterranean fever (FMF) and polyarteritis nodosa (PAN) has been well established. These patients have been reported to have an overall better prognosis than other PAN patients. Herein we report a patient with FMF and PAN who died of sepsis following a severe course of recurrent bleeding e...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-003-0424-y
更新日期:2005-01-01 00:00:00
abstract::We present a rare case of retinoid-induced sclerotic changes of lumbar spine and femur demonstrated by dual energy x-ray absorptiometrie (DEXA). The patient had flowing ossification along thoracic spine resembling diffuse idiopathic skeletal hyperostosis (DISH), but there was no ligament calcification in the lumbar sp...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-003-0391-3
更新日期:2004-09-01 00:00:00
abstract::There are numerous causes of pulmonary cavitary lesions as infection (bacterial, parasitic and invasive fungal), Wegener granulomatosis (WG) and other vasculitis, sarcoidosis, malignancy, septic thromboembolism, airways disease (cystic bronchiectasis and bullae), pneumatoceles and traumatic parenchymal laceration. Her...
journal_title:Rheumatology international
pub_type: 信件
doi:10.1007/s00296-012-2424-2
更新日期:2013-08-01 00:00:00
abstract::The aim of the study was to compare the diagnostic efficacy of the visual assessment of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences compared to the STIR sequence in the diagnostics of active sacroiliitis in the course of axial spondyloarthritis (axSpA). The study group consisted of 4...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-019-04373-x
更新日期:2019-09-01 00:00:00
abstract::We report on a 69-year-old woman who presented with myalgia, hearing impairment, fever, night sweats, weight loss, muscular weakness, paresthesia, hypesthesia, and hypalgesia. Sural nerve biopsy showed demyelinative and axonal polyneuropathy due to necrotizing vasculitis with fibrinoid necrosis. A positive test for an...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s002960000063
更新日期:2000-12-01 00:00:00
abstract:KEY MESSAGES:No difference between both hands was observed for clinical and radiographical presentations in EHOA patients. A bilateral and symmetrical relationship was found between hand joints. HIGHLIGHTS:EHOA have symmetrical distribution and specific association in structural lesions. This study aims to analyse the...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-020-04784-1
更新日期:2021-01-27 00:00:00
abstract::The assessment of skin fibrosis is vital for the diagnosis and monitoring of treatment in the systemic sclerosis (SSc)-a severe autoimmune disease. The elastography is a technique of skin fibrosis assessment through the evaluation of skin strain. We compared the efficacy of the shear wave elastography (SWE) and common...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-020-04539-y
更新日期:2020-05-01 00:00:00
abstract::This study was performed to evaluate the effects of the TNF-alpha inhibitor etanercept on oxidation stress markers representing DNA damage, lipid peroxidation, and protein glycosylation. Twenty-two rheumatoid arthritis (RA) patients underwent etanercept treatment. The levels of serum total, urinary total, and urinary ...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-007-0419-1
更新日期:2008-01-01 00:00:00
abstract::Here we evaluated whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have beneficial effects for collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type-II collagen and administered 100 mg/kg of pravastatin interperitoneally. We measured the effects of pravastatin for CIA...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-006-0270-9
更新日期:2007-05-01 00:00:00
abstract::We describe the case of a 59 year old man with systemic sclerosis and superficial siderosis of the central nervous system characterized by progressive worsening of walking with signs of pyramidal liberation associated with cerebellar ataxia and bilateral hypoacusia. Ferritin and oligoclonal bands were found on lumbar ...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-008-0523-x
更新日期:2008-06-01 00:00:00
abstract::Activation of opioid receptors on peripheral sensory nerve terminals by opioid peptides that are produced and released from immune cells can result in inhibition of inflammatory pain. This study tests the hypothesis that postoperative pain is attenuated endogenously through a local sympathetic neurotransmitter-activat...
journal_title:Rheumatology international
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00296-010-1489-z
更新日期:2011-10-01 00:00:00
abstract::The aim of the study was the thermovisual comparison of mean temperature of hand surface changes after local cryotherapy with vapors of nitrogen (-160°C) and cold air (-30°C). Forty-seven patients with rheumatoid arthritis (39 women and 8 men; average age 56.2 ± 10.5 years) were included in the study. They had the app...
journal_title:Rheumatology international
pub_type: 临床试验,杂志文章
doi:10.1007/s00296-011-2078-5
更新日期:2012-10-01 00:00:00
abstract::Macrophagic myofascitis (MMF) is an unusual inflammatory myopathy characterized by muscle infiltration by macrophages and lymphocytes. Here, we describe a case of MMF which is associated with rheumatoid arthritis. A 53-year-old Japanese rheumatoid arthritis (RA) patient presented with focal tenderness of lower extremi...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-009-1015-3
更新日期:2010-05-01 00:00:00
abstract::The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is an inclusive questionnaire, able to describe the total impairments and restrictions due to axial spondyloarthritis (axSpA). Considering the relationship between ASAS HI and the Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP,...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-016-3642-9
更新日期:2017-05-01 00:00:00
abstract::The synovial fluids (SF) of patients with rheumatoid arthritis (RA) were investigated for their effects on thymocytes of C3H/HeJ mice. Of the 20 SF tested, 17 (85%) showed an augmentation of the phytohaemagglutinin (PHA) induced thymocyte stimulation. Out of 16 SF of patients with osteoarthrosis, such an activity was ...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/BF00541245
更新日期:1982-01-01 00:00:00
abstract::Thrombocytosis is well described in children with Kawasaki disease (KD). We describe six children with KD who had thrombocytopenia at disease onset. This is an unusual finding and has clinical implications in the diagnosis of this condition. ...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-009-0947-y
更新日期:2009-12-01 00:00:00
abstract::The family name of author Francesco La Torre was incorrect in the published article. The correct family name should read as La Torre F. ...
journal_title:Rheumatology international
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00296-018-4042-0
更新日期:2018-07-01 00:00:00
abstract::Chondrocyte structure and function under the influence of two gold-containing therapeutic agents, aurothioglucose and triethylphosphine gold, were studied in a monolayer culture system for cultivating lapine articular chondrocytes. The functional parameters investigated were chondrocyte proliferation and the incorpora...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/BF00541144
更新日期:1983-01-01 00:00:00
abstract::Previous studies have shown that fibromyalgia syndrome (FMS) is associated with low level of physical activity and exercise, which may lead to an increased risk of osteoporosis. However, studies of bone mineral density (BMD) in fibromyalgia have shown conflicting results. Thus, we conducted a systematic review and met...
journal_title:Rheumatology international
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00296-016-3625-x
更新日期:2017-04-01 00:00:00
abstract::This study examines whether or not MBD4 polymorphism is a marker for rheumatoid arthritis (RA) susceptibility or severity for Chinese patients in Taiwan. This study included 193 patients with RA, while 190 unrelated healthy individuals living in Central Taiwan served as controls. The relationship between MBD4 polymorp...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-010-1545-8
更新日期:2012-01-01 00:00:00
abstract::The aim of the study was to assess the possible association between type II collagen turnover seromarkers and disease profile in patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). Outpatients with axial SpA (n = 110) or PsA (n = 101) underwent clinical examination including disease activity mea...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-015-3397-8
更新日期:2016-04-01 00:00:00
abstract::In this cross-sectional study a comparison was made of rheumatoid factor (RF) isotypes in 203 RF positive patients with arthritis. Of these, 129 had rheumatoid arthritis (RA) and 74 a milder disease that would formerly have been classified as probable RA. The majority (74%) of the RA patients had elevations of two or ...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/BF00290265
更新日期:1992-01-01 00:00:00
abstract::Osteoarthritis (OA) has a strong genetic component, and experimental evidence suggests the involvement of the Wnt pathway in its pathogenesis. Hence, we explored the association of common single nucleotide polymorphisms (SNPs) related to the Wnt pathway with hip and knee OA. Seventy-eight SNPs were analyzed in 606 pat...
journal_title:Rheumatology international
pub_type: 杂志文章
doi:10.1007/s00296-013-2821-1
更新日期:2013-11-01 00:00:00