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ID PMID Title PublicationDate abstract
24717015 The current relevance and use of prednisone in rheumatoid arthritis. 2014 May Prednisone is an old and very valuable drug in clinical use for over 60 years by now. It is well known by physicians and widely used for different kinds of inflammatory states including rheumatoid arthritis (RA). Clinical trials during the last 20 years have changed its clinical use, particularly with regards to dosage. Today, rheumatologists are treating their patients much more likely over a long period of time using a low-dose scheme. The effectiveness and safety of this low-dose use is the objective of the current clinical research and shall be enlightened in this drug profile. It is also featuring current knowledge about the value of modified-release prednisone with regards to the just published results of the 2nd Circadian Administration of Prednisone in Rheumatoid Arthritis trial. Moreover, the mechanisms of action of prednisone and its relatives will be summed up.
22589377 HDL protein composition alters from proatherogenic into less atherogenic and proinflammato 2013 Apr OBJECTIVE: An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated. METHODS: In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time. RESULTS: In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients. CONCLUSION: This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.
23916580 Isolation of xanthone and benzophenone derivatives from Cyclopia genistoides (L.) Vent. (h 2013 Oct A fast and efficient method for the isolation of the C-glucosidated xanthones mangiferin and isomangiferin from the South-African plant Cyclopia genistoides was developed for the first time. The procedure involved extraction, liquid-liquid partitioning with ethyl acetate and subsequent precipitation of mangiferin and isomangiferin from methanol and acetonitrile-water fractions, respectively. Additionally, two benzophenone derivatives: 3-C-β-glucosides of maclurin and iriflophenone, were isolated from C. genistoides extracts using semi-preparative HPLC. Apart from the above, the isolation procedure also yielded hesperidin and small amounts of luteolin. The structures of the compounds were determined by 1D and 2D NMR experiments and/or LC-DAD-ESI-MS. The selected Cyclopia constituents were screened for pro-apoptotic activity on TNF-α-stimulated synovial cells isolated from rheumatoid arthritis patients. The strongest effect, measured as percent of apoptotic cells, was recorded for isomangiferin (75%), followed by iriflophenone 3-C-β-glucoside (71%), hesperidin (67%) and mangiferin (65%). The results are encouraging for further studies on the use of the above compounds in the treatment of rheumatoid arthritis.
24518855 The diagnosis and classification of undifferentiated connective tissue diseases. 2014 Feb The term undifferentiated connective tissue disease (UCTD) refers to unclassifiable systemic autoimmune diseases which share clinical and serological manifestations with definite connective tissue diseases (CTDs) but not fulfilling any of the existing classification criteria. In this review we will go through the more recent evidence on UCTD and we will discuss in what extent the availability of new criteria for the CTDs could interfere with the "UCTD concept". The development of criteria able to identify early phases of defined CTD, may help in the differentiation of stable UCTD form their early stages and may offer a valuable guide to the treating physician to set up appropriate follow up schedules as well as therapeutic protocols. This simplified subset of CTD could offer a model to study clinic pathological correlations as well as the role of possible environmental factors in the development of autoimmunity.
25150077 The ITGAV-rs3911238 polymorphism is associated with disease activity in rheumatoid arthrit 2014 Oct Evidences indicate that angiogenesis is an important process in the development of destructive synovial tissue in rheumatoid arthritis (RA). Recently, it has been shown that the polymorphism of the integrin-αv subunit encoded by the ITGAV gene plays a role in angiogenesis and is considered as RA susceptibility loci. This study investigated association of four single nucleotide polymorphisms (SNPs) in ITGAV with disease activity score (DAS28), serum levels of C-reactive protein (CRP), and anti-cyclic citrullinated peptide(anti-CCP) antibody in 419 RA patients and 398 healthy individuals. Four SNPs in ITGAV gene (rs3911238, rs3738919, rs10174098 and rs3768777) were analyzed. Serum concentrations of anti-CCP antibody and CRP were measured by ELISA. We used the EULAR activity criteria to calculate DAS28-CRP. Among these SNPs, the ITGAV-rs3911238-G/C polymorphism was associated with RA disease activity [remission-to-low and moderate-to-high in codominant model (CC vs.GG: OR=1.53, p=0.041 and allele (C vs. G: OR=1.18, p=0.042)] and presence of anti-CCP (codominant CC vs.GG: OR=2.77, p=0.001, allele C vs. G: OR=1.19,p=0.033). The carriers of CC genotype ITGAV-rs3911238 had higher serum levels of CRP and anti-CCP antibody titer and higher ESR and disease activity score than carriers of GG and CG genotypes. Furthermore, haplotypes analysis showed that ITGAV rs3733891C/rs3768777T/rs3911238C/rs10174098A and ITGAV rs3733891A/rs3768777T/rs3911238G/rs10174098A haplotypes increased severity and anti-CCP antibody in RA patients (OR=5.54, p=0.049 and OR=2.89; p=0.024, respectively) in comparison with ITGAV rs3733891C/rs3768777T/rs3911238G/rs10174098A haplotypes. Thus, the present study demonstrated that the link between systemic inflammatory markers and the ITGAV-rs3911238 polymorphism allele in Iranian RA patients.
24862493 Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund׳s adjuvant i 2014 Aug 8 ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium strumarium L. fruit (Xanthiu fruit) has been traditionally used as a medicinal herb in China for the treatment of many ailments including rheumatoid arthritis. However, the anti-arthritic activity of Xanthium strumarium fruit has still not been demonstrated. In the present study, we confirmed that the extract of Xanthium strumarium (EXS) prevents rheumatoid arthritis induced by Complete Freund׳s Adjuvant (CFA) in rats. MATERIALS AND METHODS: Male Wistar rats (160±10 g) were immunized by intradermal injection of 0.1 mL of CFA into the left hind metatarsal footpad. EXS was administered orally at a dose of 300 and 75 mg/kg once a day after the induction of adjuvant arthritis. Methotrexate (3 mg/kg, twice a week) was used as a positive control. Paw swelling, arthritic score, body weight loss, spleen index, thymus index, serum cytokines, inflammatory mediators and histological change were measured. The chemical profile of EXS was analyzed by HPLC-DAD. RESULTS: We found that the EXS significantly suppressed paw swelling and arthritic score, increased body weight loss and decreased the thymus index. The overproduction of TNF-α and IL-1β were remarkably suppressed in the serum of all EXS-treated rats, and in contrast IL-10 was markedly increased. The level of COX-2 and 5-LOX was also decreased with EXS treatment. Ten phenolic acid derivatives were identified from 14 detected peaks by HPLC-DAD with the reference substances and verified by LC-MS. CONCLUSIONS: These results suggest the potential effect of EXS as an anti-arthritis agent towards CFA-induced arthritis in rats. Xanthium strumarium has the potential to be regarded as a candidate for use in general therapeutics and as an immune-modulatory medicine in rheumatoid arthritis.
23981747 Disease patterns of rheumatology outpatients seen in a tertiary hospital serving a multi-e 2013 Jun AIMS: To describe the spectrum of diseases seen in an outpatient setting in the Singapore General Hospital, the largest tertiary referral centre in Singapore. METHODS: In this cross-sectional study, medical records of patients scheduled for an appointment at the rheumatology specialist outpatient clinics over a 4-month period (10 August 2010-31 December 2010) were reviewed. Primary diagnoses documented by the attending physician at the latest visit were recorded. RESULTS: Among 4180 patients (29.5% male; mean [SD] age: 53.5 [15.1] years; 77.0% Chinese, 8.0% Malay, 8.8% Indian and 6.2% others), the spectrum of diseases seen was as follows [disease - definite n (%), probable n (%)]: Arthritis: rheumatoid arthritis - 958 (22.9%), 68 (1.6%); osteoarthritis - 452 (10.8%), 39 (0.9%); crystal arthritis - 417 (10.0%), 18 (0.4%); spondyloarthritis - 227 (5.4%), 61 (1.5%); psoriatic arthritis - 158 (3.8%), 9 (0.2%); other inflammatory arthritis - 153 (3.7%), 94 (2.2%); Connective tissues diseases: systemic lupus erythematosus - 412 (9.9%), 26 (0.6%); vasculitis - 105 (2.5%), 22 (0.5%); Sjögren's syndrome - 81 (1.9%), 32 (0.8%); overlap syndromes - 73 (1.8%); scleroderma - 50 (1.2%), 4 (0.1%); undifferentiated connective tissue diseases - 45 (1.1%), 106 (2.5%); myositis - 41 (1.0%), 12 (0.3%); antiphospholipid syndrome - 22 (0.5%), 7 (0.2%); polymyalgia rheumatica - 16 (0.4%); Others: soft tissue rheumatism - 155 (3.7%); osteoporosis - 61 (1.5%); other non-rheumatologic conditions - 189 (4.5%); other rheumatologic conditions - 67 (1.6%). CONCLUSION: Rheumatoid arthritis, osteoarthritis and crystal arthritis were the three most common rheumatological diseases seen in a tertiary referral centre serving a multi-ethnic urban Asian population in Singapore.
23329683 Rate of adjudication of radiological progression in rheumatoid arthritis randomized contro 2013 Aug OBJECTIVE: The aim of this study is to provide data on the adjudication rate for a predetermined threshold of difference in change score between two readers in randomized controlled trials (RCTs). METHODS: Fifteen datasets from RCTs in RA were scored by 13 experienced readers as pairs according to the modified Sharp-van der Heijde method. The theoretical adjudication rates for thresholds of between 3 and 20 units were calculated. We investigated the influence of the number of time points within the same session, the length of the interval and disease duration on the adjudication rates. RESULTS: A total of 21,295 time points from 7643 patients from 15 databases were included in the analysis. The adjudication rate was inversely related to the threshold. Higher adjudication rates were observed with a higher number of time points, longer time intervals and in early versus established RA. The adjudication rates ranged from 0% to 22% depending on the scenario. CONCLUSION: With trained and experienced readers, the adjudication rate in RA RCTs is low even with very conservative adjudication thresholds.
24077913 Anti-TNF therapy in patients with HBV infection--analysis of 87 patients with inflammatory 2014 Jan This study aims to investigate the incidence of hepatitis B virus (HBV) reactivation in inflammatory arthritis (IA) patients with HBV infection using anti-tumor necrosis factor (TNF) agents and evaluate the efficacy of antiviral therapy in reducing the risk of viral reactivation in chronic HBV infection. IA patients using anti-TNF agents from six centers were enrolled. Their HBV infection conditions and ALT and HBV-DNA levels were monitored periodically. Among the six chronic hepatitis B patients, HBV reactivation was found in two patients without antivirus prophylaxis and no viral replication was detected in the other four patients with antivirus prophylaxis. In the 31 inactive carriers, the increase of viral load was detected in 6 of 22 (27.3 %) patients without antiviral prophylaxis, and there was no viral reactivation in the other 9 patients with antiviral prophylaxis. HBV reactivation was not found in the 50 patients with resolved HBV infection. It is suggested that anti-TNF therapy might increase the risk of HBV reactivation in patients with chronic HBV infection, and antiviral prophylaxis could effectively decrease the risk. Anti-TNF agents seem to be safe in patients with resolved HBV infection.
25295757 Associations between Klinefelter's syndrome and autoimmune diseases: English national reco 2015 Mar There are reports suggesting that people with Klinefelter's syndrome (KS) may be at increased risk of some autoimmune diseases, but the evidence is not substantial. We wanted to add to the evidence by systematically assessing the risk of autoimmune diseases in a national cohort of people with KS. We selected records of all people with KS in a record-linked dataset of all hospital day cases and inpatient admissions in England, 1999-2011; and we followed them up by electronic record linkage to identify the occurrence of autoimmune diseases. We compared their occurrence in the KS cohort with a control cohort, studied in the same way, and expressed the results as rate ratios (RR). Of 30 autoimmune diseases studied in people with KS, there were significantly increased risks of seven-Addison's disease (RR 11.7, 95% confidence interval 2.4-34.4), diabetes mellitus type 1 (6.1, 4.4-8.3), multiple sclerosis (4.3, 1.2-11.0), acquired hypothyroidism (2.7, 1.8-4.0), rheumatoid arthritis (3.3, 2.0-5.2), Sjogren's syndrome (19.3, 4.0-57.0) and systemic lupus erythematosus (18.1, 2.2-65.6). We concluded that people with KS have increased risk of some autoimmune diseases, particularly those that are female-predominant. The increased risk of autoimmune diseases associated with the XXY karyotype may hold clues to the pathogenesis of some aspects of autoimmunity.
25222933 Expression of the inherently autoreactive idiotope 9G4 on autoantibodies to citrullinated 2014 BACKGROUND: The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific 'parent' B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA. METHODOLOGY/PRINCIPAL FINDINGS: Sera from 19 patients with established RA and those with <1year history of untreated polyarthritis either resolving into RA (n = 42) or non-RA diagnosis (n = 31) were included. Autoantibodies to cyclic citrullinated peptides (CCP), RhF and co-expression of the 9G4 idiotope were measured by ELISA. 9G4 recognised a population of anti-CCP antibodies in the majority of sera from patients with established disease and also in samples from patients with early disaese. 9G4+RhF levels were generally lower and not associated with positivity for, or levels of 9G4+CCP. CONCLUSIONS/SIGNIFICANCE: The persistence of 9G4+ immunoglobulins, of any isotype, in serum is rare. We describe here the novel finding of 9G4 expression on anti-CCP antibodies in patients from the earliest symptoms of RA through to established disease. Our results suggest that 9G4 expression on anti-CCP autoantibodies was not due to polyclonal expansion of VH4-34-encoded immunoglobulins. These studies may therefore provide a new focus for investigation into the evolution of the autoimmune response in RA patients.
24025028 Revision of a failed Swanson arthroplasty to a total wrist replacement restores wrist func 2014 Apr This study reports a case of revision of a failed Swanson silastic interpositional wrist replacement to a Universal 2 (KMI Medical Inc., San Diego, CA, Jan 2009) total wrist arthroplasty, in a 68-year-old woman with rheumatoid arthritis and pyrophosphate arthropathy. At the 2-year follow-up, the patient was pain-free and was able to perform all activities of daily living, documented by subjective assessment and objective scores. The disabilities of the arm, shoulder, and hand (DASH) scores improved from 98.3 preoperatively to 55.1 postoperatively. A failed Swanson silastic interpositional wrist replacement may be successfully revised to an uncemented primary wrist replacement with good functional results at early follow-up.
24407907 Pain threshold and intensity in rheumatic patients: correlations with the Hamilton Depress 2015 Mar Individuals suffering from chronic pain are frequently affected by depression, which in turn increases the risk of developing chronic pain over time. This study aims to investigate the relationship between depression and pain intensity and threshold in a group of rheumatic patients compared to healthy subjects. One hundred twenty-four individuals of whom 50 were affected by rheumatoid arthritis (RA), 23 by psoriatic arthritis (PsA), 23 by ankylosing spondylitis (AS), and 28 age-matched controls without chronic pain underwent quantitative sensory testing to assess pressure pain threshold with pressure algometry. Pain intensity was evaluated through the visual analogue scale (VAS) and depression through the Hamilton Depression Rating scale (HAMD). A significant inverse correlation between HAMD values and pressure pain thresholds was found in the entire group of patients (p < 0.0001), in controls (p = 0.02), and also in RA (p = 0.002), PsA (p < 0.0002), and AS (p = 0.02) patients when analyzed separately, while no significant correlation was found between HAMD and VAS values or pressure pain thresholds and VAS. We found lower pain thresholds in RA and PsA patients while no difference has been evidenced in AS patients compared to healthy controls. HAMD scores were also significantly higher in rheumatic patients than in controls. The use of pressure algometry in the evaluation of chronic pain in patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis that display comorbid depression could represent an additional and integrative method to improve pain/depression overlap management or research.
23179005 Leflunomide in dialysis patients with rheumatoid arthritis--a pharmacokinetic study. 2013 Feb Pharmacokinetic data of disease modifying antirheumatic drugs during hemodialysis are limited to sulfasalazine, methotrexate, and cyclosporine. Only respective anecdotal data have been reported on leflunomide. We repeatedly measured teriflunomide (A77-1726), the active metabolite of leflunomide, during standard hemodialysis sessions and calculated teriflunomide clearances in five patients with rheumatoid arthritis (RA) and end-stage renal disease. The calculated teriflunomide clearances during a standardized dialysis session of 3-4.5 h at a blood flow rate of 160-300 ml/min were between 0 and 4.3 ml/min, the mean clearances of the total dialysis ranged between 1.1 and 3.4 ml/min. Total amount of teriflunomide removed was 5.8-8.8 μg per dialysis session. Dialytic removal of the active metabolite of leflunomide, teriflunomide (A77-1726), is negligible. Leflunomide can be used for RA patients on chronic dialysis without any dosage modification.
25249533 [Is cobalt-binding capacity of serum a new perspective diagnostic marker?]. 2014 Jul The aim of this study was to determine the reference interval of serum cobalt-binding capacity (CoBC) and to estimate the effect of factors unrelated to oxidative modification of serum albumin on this diagnostic marker. A group of healthy volunteers (n=194), a group of patients with autoimmune diseases (n=44) and a group of patients with diabetes type 2 (n=50) participated in this study. The regional reference interval was found to be 0,462-0,744 mmol Co 2+ /l of serum. The study of serum CoBC in two groups of patients showed that the CoBC level strongly depends on the serum protein profile. Therefore, this diagnostic test may be used for diagnosing ischemia, but other pathologies associated with changes in a ratio of blood protein fractions can also influence the serum CoBC level.
23311967 Elevated serum and synovial fluid TNF-like ligand 1A (TL1A) is associated with autoantibod 2013 OBJECTIVES: Tumour necrosis factor (TNF)-like ligand 1A (TL1A) is involved in rheumatoid arthritis (RA) but its clinical relevance in RA has not been fully elucidated. We analysed TL1A levels in the serum and synovial fluid (SF) of RA patients and investigated its clinical significance. METHODS: TL1A levels were measured by enzyme-linked immunosorbent assay (ELISA) in 109 RA patients, 29 patients with osteoarthritis (OA), and 126 healthy controls. Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The associations between TL1A and the clinical and serological features of RA were analysed. RESULTS: TL1A concentrations were significantly elevated in both serum and SF of RA patients compared with OA patients and healthy controls. TL1A levels in RA SF were significantly higher than those in matched serum. A positive correlation was found between SF and serum TL1A levels. Serum TL1A concentrations were associated with RA-specific autoantibodies including RFs (RF-IgG, RF-IgM) and anti-citrullinated protein antibodies. Antibody production by peripheral blood mononuclear cells (PBMCs) from RA patients was elevated upon TL1A stimulation. However, there was no correlation between serum or SF TL1A levels and RA disease activity. CONCLUSIONS: TL1A levels are significantly elevated in RA serum and SF and positively correlated with autoantibody production in RA, but failed as a disease activity marker. TL1A promotes antibody production by PBMCs from RA patients. The role of TL1A in the humoral autoimmune response may be important in the development of RA.
23161899 Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment 2013 May BACKGROUND: Mitogen-activated protein (MAP) kinases are key regulators of cytokine production, and are therefore potential targets for treatment of rheumatoid arthritis (RA). OBJECTIVE: This two-part phase II study investigated the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP kinase-activated protein kinase 5) dose vs placebo (part A). An interim analysis after part A would determine whether the dose-finding part (part B) would be performed. METHODS: In part A, eligible methotrexate (MTX)-refractory patients with RA were randomised to receive either a once-daily 50 mg dose of GLPG0259 or placebo, in addition to a stable dose of MTX, for 12 weeks. The primary efficacy end point was the percentage of patients achieving an American College of Rheumatology 20% improvement (ACR20) response after 12 weeks. RESULTS: The interim analysis showed no difference between the percentage of subjects achieving the primary efficacy variable of ACR20 or the secondary efficacy variables (ACR50, ACR70 and Disease Activity Score 28) at week 12 in the GLPG0259-treated (n=19) and placebo-treated (n=11) groups. Owing to lack of efficacy, the study was terminated, and part B was not initiated. CONCLUSIONS: This innovative study design quickly provided conclusive results on the lack of efficacy of GLPG0259 in patients with RA.
25112460 Therapeutic options after treatment failure in rheumatoid arthritis or spondyloarthritides 2014 Aug The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy.
24378059 [Effect of selective phosphodiesterase 4 inhibitors on nuclear factor kappa B, tumor necro 2013 Oct OBJECTIVE: To investigate the effect of selective phosphodiesterase (PDE) 4 inhibitors on nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNFα) and interleukin-8 (IL-8) secreted by peripheral blood mononuclear cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD). METHODS: PBMCs isolated from 15 healthy volunteers (group A) and 20 patients with untreated active RA-ILD (group B) were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment: blank group (B1), theophylline group (B2), selective PDE4 inhibitor rolipram group (B3), and glucocorticoid group (B4) with dexamethasone. The expression of NF-κB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: (1) The activity of NF-κB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A (P < 0.01). Compared with group B1, three parameters above were similar to those in group B2 (P > 0.05), while group B3 and group B4 had significant decreased levels of three parameters (P < 0.01); IL-8 level in group B4 was significantly lower than that in group B3 (P < 0.05). (2) TNFα and IL-8 levels were positively correlated with NF-κB activity in group B (r = 0.902 and 0.735, P < 0.01 respectively). (3) The reduction of TNFα and IL-8 levels were positively correlated with reduction of NF-κB activity after intervention of rolipram in group B3 (r = 0.874, P < 0.01; r = 0.561, P < 0.05 respectively). CONCLUSION: NF-κB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDE4 inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor NF-κB in PBMC, thus inhibiting the inflammatory reaction of RA-ILD.
24599913 Increased phosphorylation of ezrin is associated with the migration and invasion of fibrob 2014 Jul OBJECTIVE: Increasing evidence indicates that the cytoskeletal protein ezrin may play a critical role in cell motility. This study aims to investigate the role of ezrin in regulating the migration and invasion of fibroblast-like synoviocytes (FLSs) from patients with RA. METHODS: Synovial tissues were obtained from 12 patients with RA and 6 with OA, and then FLSs were separated from synovial tissues. The expression of ezrin and phosphorylated ezrin (p-ezrin) was examined by Western blotting or IF staining. A specific inhibitor of ezrin phosphorylation and small interference RNA-mediated ezrin knockdown were used to inhibit the phosphorylation of ezrin. Migration and invasion of FLSs in vitro were measured by the Boyden chamber assay. RESULTS: Increased expression of p-ezrin protein was found in synovial tissue and FLSs in patients with RA compared with patients with OA. Stimulation with TNF-α and IL-1β increased ezrin phosphorylation in RA FLSs. Inhibition of p-ezrin protein by a specific inhibitor of phosphorylation of ezrin and small interfering RNA-mediated knockdown reduced in vitro migration and invasion, as well as actin stress fibre formation in RA FLS. Furthermore, rho kinase and p38 mitogen-activated protein kinase (MAPK) signal pathways were involved in the phosphorylation of ezrin and invasion of RA FLSs. CONCLUSION: Increased expression of p-ezrin may contribute to aberrant aggressive behaviours of RA FLSs, which are mediated by rho kinase and the p38 MAPK pathway. This suggests a novel strategy targeting phosphorylation of ezrin to prevent synovial invasiveness and joint destruction in RA.