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ID PMID Title PublicationDate abstract
27458622 [Cardiovascular disease in rheumatic diseases]. 2016 The representatives of immunoinflammatory diseases are rheumatic ones, such as primarily rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, and other systemic connective diseases, which are characterized by a high risk for untimely death. The high risk of untimely death in these diseases has been found to be associated with the severity of an immunoinflammatory process that gives rise to severe irreversible damage to vital organs and systems and with the development of a wide spectrum of comorbidities (infections, interstitial lung disease, malignant tumors, osteoporotic fractures, etc.). Among them, diseases of the cardiovascular system, which are most commonly caused by the early development and.accelerated progression of atherosclerotic coronary lesions, hold a central.position. The paper gives the data available in the recent literature on the impact.of antirheumatic therapy (disease-modifying antirheumatic drugs and biological agents) on' the cardiovascular system.
27323035 Diagnostic performance of anti-citrullinated protein/peptide antibodies in juvenile idiopa 2016 May 13 The prevalence rates of anti-citrullinated protein/peptide antibodies (ACPAs) were investigated in a cohort of juvenile idiopathic arthritis (JIA) patients, and their diagnostic performances were compared. ACPAs, including anti-cyclic citrullinated peptide IgG (anti-CCP), anti-CCP IgG/IgA (anti-CCP3.1), citrullinated recombinant rat filaggrin antibodies (CPA), anti-mutated citrullinated vimentin (anti-MCV), and antibodies to citrullinated human IgG-derived peptides (RA/CP), were measured in the sera from 81 JIA patients. Serum samples from 55 children with other joint diseases or viral infections and 49 healthy donors were tested as controls. Of the 81 JIA patients, 7 (8.6%), 8 (9.9%), 17 (21.0%), 23 (28.4%), and 18 (22.2%) were found to be positive for anti-CCP, anti-CCP3.1, CPA, anti-MCV, and RA/CP, respectively, with specificities of 98.1, 95.1, 93.3, 84.6, and 86.5%. Analysis by subtype revealed that 7/7 (100%) of RF-positive polyarticular JIA patients tested positive at high serum levels for anti-MCV or RA/CP, and 5/7 (71.4%) were positive for anti-CCP, anti- CCP3.1, or CPA (P < 0.001, compared with controls). Eighteen of 81 JIA patients demonstrated joint erosions on radiographs and erosive arthritis occurred more often in ACPAs positive patients (P < 0.01). Our findings indicate that although ACPAs are not satisfactory screening biomarkers for JIA due to low sensitivity, ACPA measurement can aid in diagnosing RF-positive polyarticular JIA and identifying JIA patients with severe bone involvement. The diagnostic performance of each ACPA in JIA is different, and the careful selection of assays is necessary.
27457366 Anti-MCV and anti-CCP antibodies-diagnostic and prognostic value in children with juvenile 2016 Nov The goal of the study was to evaluate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) antibodies in juvenile idiopathic arthritis (JIA) comparing to anti-cyclic citrullinated peptide (anti-CCP). Thirty children with confirmed JIA diagnosis and 20 children as a control group were included into the study. Serum and synovial fluid levels of anti-CCP, anti-MCV, and immunoglobulin M rheumatoid factor (IgM-RF) antibodies have been assessed. Anti-MCV was positive in 11/30 (36.6 %), whereas anti-CCP positivity was found in 12/30 (40 %) children with JIA. Among 11 children with JIA positive for anti-MCV, five (45.5 %) were also positive for anti-CCP and among 18 JIA children negative for anti-CCP, six (33.33 %) were also anti-MCV positive. Six out of 30 JIA children were found to be IgM-RF positive. In general, two out of all those 11 anti-MCV-positive patients demonstrated oligoarthritis and 9/11 had polyarticular type of onset. Anti-MCV serum concentration correlated positively with anti-CCP (p = 0.004). Almost 60 % of children in early stage of JIA were anti-MCV positive. Levels of anti-CCP antibodies correlated positively with the disease activity (p = 0.0014) and radiological outcome (p = 0.00017). In all synovial fluid samples, the concentration of autoantibodies was under the cut-off values. The results of our study indicate that anti-MCV as well as anti-CCP antibodies may be helpful in the diagnosis of JIA, especially in the early course of the disease. Anti-MCV antibodies could identify a group of children with JIA which is negative for anti-CCP antibodies and RF. However, it appears that in JIA, anti-CCP rather than anti-MCV antibodies have impact on radiographic changes.
26221077 Norisoboldine, an Anti-Arthritis Alkaloid Isolated from Radix Linderae, Attenuates Osteocl 2015 Norisoboldine (NOR), the primary isoquinoline alkaloid constituent of the root of Lindera aggregata, has previously been demonstrated to attenuate osteoclast (OC) differentiation. Accumulative evidence has shown that aryl hydrocarbon receptor (AhR) plays an important role in regulating the differentiation of various cells, and multiple isoquinoline alkaloids can modulate AhR. In the present study, we explored the role of NOR in the AhR signaling pathway. These data showed that the combination of AhR antagonist resveratrol (Res) or α-naphthoflavone (α-NF) nearly reversed the inhibition of OC differentiation through NOR. NOR could stably bind to AhR, up-regulate the nuclear translocation of AhR, and enhance the accumulation of the AhR-ARNT complex, AhR-mediated reporter gene activity and CYP1A1 expression in RAW 264.7 cells, suggesting that NOR might be an agonist of AhR. Moreover, NOR inhibited the nuclear translocation of NF-κB-p65, resulting in the evident accumulation of the AhR-NF-κB-p65 complex, which could be markedly inhibited through either Res or α-NF. Although NOR only slightly affected the expression of HIF-1α, NOR markedly reduced VEGF mRNA expression and ARNT-HIF-1α complex accumulation. In vivo studies indicated that NOR decreased the number of OCs and ameliorated the bone erosion in the joints of rats with collagen-induced arthritis, accompanied by the up-regulation of CYP1A1 and the down-regulation of VEGF mRNA expression in the synovium of rats. A combination of α-NF nearly completely reversed the effects of NOR. In conclusion, NOR attenuated OC differentiation and bone erosion through the activation of AhR and the subsequent inhibition of both NF-κB and HIF pathways.
25603035 Treating to target in psoriatic arthritis. 2015 Mar PURPOSE OF REVIEW: Psoriatic arthritis (PsA) is an inflammatory arthritis causing significant joint damage and impaired quality of life. A treat to target approach has revolutionized the care of patients with rheumatoid arthritis over the last decade. There is now increasing interest in a similar approach in PsA, as it seems that ongoing joint inflammation predicts subsequent damage and loss of function. RECENT FINDINGS: A 2011 European League Against Rheumatism review highlighted a lack of evidence for treat to target in PsA. However, with the development of the minimal disease activity criteria, a target is available and preliminary results from the first randomized treat-to target study (Tight Control of PsA Study) using these criteria have shown significant benefit in joint and skin disease activity and patient-reported outcomes. SUMMARY: Early evidence has shown the potential benefit of a treat-to-target approach in PsA and further research is needed to optimize treatment pathways for all subtypes of the disease.
25802789 A case of multicentric carcinoid in a patient with psoriatic spondyloarthropathy. 2015 We describe the first case of a patient presenting with multicentric carcinoid occurring in the lung and subsequently in the rectum, with chronic psoriatic arthritis. Although reports have been published regarding carcinoid syndrome occurring alongside rheumatoid arthritis, no reports have been made on such a case. Initial presentation of carcinoid syndrome in this patient was insidious and atypical with few symptoms, including shortness of breath and long standing abdominal bloating. Several years later a sudden change in bowel habit prompted a colonoscopy with biopsy that revealed a carcinoid rectal polyp. The case we report describes a rare presentation of carcinoid syndrome in chronic psoriatic arthropathy.
27658047 A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Respons 2016 The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses. Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases.
27158245 The synthetic cannabinoid WIN55,212-2 mesylate decreases the production of inflammatory me 2016 BACKGROUND: In rheumatoid arthritis (RA), synovial fibroblasts (SF) secrete large amounts of IL-6, IL-8 and matrix metalloproteinases (MMPs) which are crucial for cartilage destruction. RASFs are sensitive to the action of cannabinoids and they not only express cannabinoid receptors type I and II (CB1 and CB2) but also transient receptor potential channels type vanilloid (TRPV1) and ankyrin (TRPA1). The synthetic cannabinoid WIN55,212-2 mesylate (WIN) demonstrated strong anti-inflammatory effects in monocytes and synovial fibroblasts only in high concentrations in a non-cannabinoid receptor dependent manner. In this study we assessed the ability of WIN to modulate cytokine and MMP-3 production in SFs over a wide concentration range and identified specific receptor targets that mediate the effects of this synthetic cannabinoid. METHODS: MMP-3, IL-6 and IL-8 were determined by ELISA. Adhesion was measured by the XCELLigence system. Proliferation was assessed by cell titer blue assays. RESULTS: WIN significantly reduced TNF-induced IL-6, IL-8 and MMP-3 production in concentrations below 2 μM, while higher concentrations completely inhibited production of IL-6 and IL-8 but increased extracellular MMP-3 levels. The inhibitory effect at low concentrations (<2 μM) was independent on activation of either CB1 or CB2 but was attenuated by TRPV1 or TRPA1 inhibition in OASFs and RASFs. The effects of high concentrations of WIN on cytokine and MMP-3 production were decreased by the calcium chelating agent BAPTA, the AMPK activator metformin, the TRPA1 antagonist A967079 and the CB2 antagonist COR170. Furthermore, fetal calf serum content in culture media strongly influenced the efficacy of WIN at high concentrations. In addition, high concentrations of WIN also diminished SF adhesion and proliferation without altering cell viability whereas low concentrations promoted SF adhesion without any influence on proliferation. CONCLUSION: The synthetic cannabinoid WIN in low concentrations exhibits anti-inflammatory effects in synovial fibroblasts independent of CB1 and CB2 while CB2 and yet unidentified receptor targets are responsible for WIN effects in micromolar concentrations. Our results indicate a TRPV1/TRPA1 dependent mechanism of SF regulation that might be coupled to cellular energy status and calcium content.
25861246 The protective effects of chronic intermittent hypobaric hypoxia pretreatment against coll 2015 OBJECTIVE: To explore the immunological mechanisms underlying the effect of chronic intermittent hypobaric hypoxia (CIHH) pretreatment on collagen-induced arthritis (CIA) in rat. METHODS: Fifty-four adult male Sprague-Dawley rats were used in the experiment. Arthritis in CIA rats (n=18) was induced by injection of collagen. The CIHH+CIA rats (n=18) were treated with CIHH (simulated 3000 m altitude, 5 hours per day for 28 days, PO2=108.8 mmHg) before CIA. The control rats (n=18) were not given any treatment. RESULTS: (1) Incidence rate of CIA in CIHH+CIA rats was significantly lower than that in CIA rats (P<0.05). (2) The paw thickness and arthritis index (AI) value in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (3) The hyperplasia with inflammatory infiltration in synovial tissue of joints in CIHH+CIA rats was much alleviative compared with CIA rats. (4) TNF-α, IFN-γ, IL-4 and IL-17 in synovial tissue of joint and serum in CIHH+CIA rats were decreased compared with CIA rats (P<0.05). (5) The number of CD4-positive T-lymphocytes and the ratio of CD4/CD8 T-lymphocytes in peripheral blood in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (6) The protein expression of HIF-1α and NF-κB in synovial tissue of joint in CIHH+CIA rats was decreased compared with CIA rats (P<0.05). CONCLUSION: CIHH pretreatment has a protective effect against collagen-induced arthritis in rat through down-regulation of HIF-1α and NF-κB, inhibition of inflammatory cytokines TNF-α and IL-17, and balance in CD4/CD8 and Th1/Th2 T lymphocytes.
26678914 The role of synthetic drugs in the biologic era: therapeutic strategies for treating juven 2016 INTRODUCTION: Juvenile idiopathic arthritis is the most frequent chronic rheumatic disease in childhood. Synthetic disease modifying drugs (DMARDs) have been used in its treatment since the 1980s and have led to substantial improvement of quality of life and disease outcome. Recent pharmacological research has focused on newer medications, especially biologic agents. AREAS COVERED: Synthetic DMARDS, especially methotrexate, rightfully remain the first-line treatment of most categories of juvenile arthritis, as attested by several international guidelines. A substantial body of evidence supports these medications, and recent research tries to clarify their optimal use in the clinical setting, both as monotherapy and in combination with biologics. In addition, new forms of synthetic DMARDs are in the research pipeline, or are already used for rheumatoid arthritis. EXPERT OPINION: Methotrexate remains the preferred first-line medication for polyarticular arthritis, with leflunomide as a viable alternative in case of intolerance or toxicity, despite lack of approval in Europe and the US. Sulfasalazine and hydroxychloroquine are used only rarely in clinical practice, considered in combination with methotrexate if biologics are not available. New synthetic DMARDS are in the research pipeline for JIA, in the form of small molecules.
26425146 Making the next steps in psoriatic arthritis management: current status and future directi 2015 Oct Psoriatic arthritis (PsA) is a chronic inflammatory condition with articular and extra-articular manifestations: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease. It is associated with cardiovascular comorbidities. It is now recognized as a new entity, different from rheumatoid arthritis and other spondyloarthritis in terms of clinical manifestations, pathogenesis, and response to therapies. Anti-tumor necrosis factors (anti-TNFs) have demonstrated clinical efficacies exceeding that of conventional disease modifying antirheumatic drugs (DMARDs). The current treatment paradigms recommend early diagnosis and treatment, and a strategic and target orientated approach, aiming at a low disease activity status. New understanding in the immunopathogenesis of PsA has led to new treatment targets. This review addresses the evidence of current treatment for each of the domains as an aid to the clinician managing these patients in the clinic. Some new therapeutic targets are presented. We highlight the importance of development and validation in outcome measures, including that of composite scores that capture various disease domains that will facilitate future clinical trials to inform the best treatment.
26441062 Joint involvement secondary to Epstein-Barr virus. 2016 Mar We describe a group of patients with Epstein-Barr virus (EBV) infection and joint involvement. Between February 2011 and January 2012, there were six cases in our unit. Two presented with a pattern similar to rheumatoid arthritis, three had polyarthralgia with an inflammatory pattern and only one patient had asymmetrical oligoarthritis of large joints. They were all women aged between 25 and 75 (4 were of child-bearing potential). Diagnosis in all the cases was made by exclusion of other possible causes and negative IgM were obtained for the rest of the "Herpesviridae" family viruses. In our series, EBV joint involvement was more common in women of childbearing potential. Clinical presentation was heterogeneous but was predominantly in the form of inflammatory joint pain. When it presents in the form of symmetrical polyarthritis, it can become chronic and require the use of disease-modifying anti-rheumatic drugs.
25800215 Cellular imaging in rheumatic diseases. 2015 Jun Developments in cellular imaging now enable the real-time visualization of the choreographed sequence of events that underlie the development of immune responses in vivo. The previously unappreciated dynamics and anatomical context of cellular interactions, revealed in these studies, can have profound consequences for the 'decision' by the immune system to induce immunological priming versus immunological tolerance. Importantly, dysregulation of this balance can result in autoimmune diseases such as rheumatoid arthritis (RA). By further developing our understanding of how, where and when cells interact during immune responses, we can further dissect these events to assess how cell interactions might be aberrant in autoimmunity. A better knowledge of the mechanisms involved in cellular interactions by means of cellular imaging can help the development and targeting of therapies to particular disease stages and tissues in patients with RA in efforts to restore immune homeostasis.
27539792 Overexpression of the transmembrane carbonic anhydrase isoforms IX and XII in the inflamed 2016 Juvenile idiopathic arthritis (JIA) is the most common form of chronic rheumatic disease affecting children worldwide, with some features similar to adult rheumatoid arthritis (RA). In the present study, we aim at investigating novel markers that will allow in the future for tailored, more personalized treatment strategies. Hence, taking notice of several reports proving the role of local acidosis as a causal link between inflammatory diseases and related pain, and the involvement of several carbonic anhydrases (CA, EC 4.2.1.1) isoforms in articular diseases, we evaluated in JIA patients the expression of these metalloenzymes. We identified that JIA patients show high levels of active CA IX and XII isoforms. Our results represent the first evidence of the identification of these enzymes as potential therapeutic targets and development of novel innovative therapies for arthritis, also considering that the two isoforms are validated antitumor targets.
25980318 Increased incidence of Sjogren's syndrome in systemic sclerosis: A nationwide population s 2015 In the past, there were no studies to evaluate the incidence of Sjogren's syndrome and its relationship with sex and age in patients with systemic sclerosis. In this study, we enrolled 2217 patients with systemic sclerosis and 6485 controls from Taiwan's Registry of Catastrophic Illness database and National Health Insurance Research Database. Every patient with systemic sclerosis was matched to at most three controls by sex, age, month, and year of first diagnosis of systemic sclerosis. Standardized incidence ratio (SIR) of Sjogren's syndrome in patients with systemic sclerosis and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). Both male and female patients with systemic sclerosis had higher incidences of Sjogren's syndrome (SIR: 7.59, 95% CI = 2.97-19.51; SIR: 7.59, 95% CI = 5.56-10.42, respectively). The incidence of Sjogren's syndrome in patients with systemic sclerosis was still higher compared with control when stratified according to age. Age at diagnosis of Sjogren's syndrome was earlier in patients with systemic sclerosis in both male and female groups (p = 0.018; p < 0.001, respectively). Systemic sclerosis was associated with Sjogren's syndrome after adjusting for age, sex, and various autoimmune diseases (HR: 5.98, 95% CI = 4.79-7.47, p < 0.001). Common cytokines, overlapping antibodies, and similar risk alleles were all potential causes of increased incidence of Sjogren's syndrome in systemic sclerosis.
28042126 B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Sy 2017 Jan OBJECTIVE: To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS). METHODS: Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed. RESULTS: In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21-producing and IL-17-producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores and serum IgG levels. CONCLUSION: B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.
26380323 Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren's Syndrome Immunopa 2015 The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren's syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/β and pIKKγ were both negative. And pIKKε positively related to expression of p-p65. Furthermore, pIKKε and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγ and IκBα between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKε expression and deregulation of NF-κB pathway.
25941062 Association of BAFF and IL-17A with subphenotypes of primary Sjögren's syndrome. 2016 Jul AIM: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting exocrine glands. Both autoreactive T cells and B cells are involved in the development of pSS, but their exact contribution to the pathogenesis is not clear. Here, we aimed to investigate the association of B-cell activating factor (BAFF) and interleukin (IL)-17A with subphenotypes of pSS. METHODS: Peripheral blood samples were collected from 31 pSS patients and 28 healthy controls. The serum levels of BAFF and IL-17A were quantified by sandwich ELISA. RESULTS: The increased circulating BAFF levels are associated with higher immunoglobulin G (IgG) levels (P = 0.0167) and anti-Ro/SS antigen A autoantibody (P = 0.032), while the elevated circulating levels of IL-17A are associated with lower C3 levels (P = 0.0213) and higher focus score of salivary gland tissue (P = 0.002). CONCLUSION: Our results show that BAFF and IL-17A are associated with different subphenotypes of pSS, suggesting both humoral and cellular immune response are involved in the pathogenesis of pSS.
27613139 Expression of type III interferons (IFNλs) and their receptor in Sjögren's syndrome. 2016 Dec Type III interferons (IFNs) or IFN-λs (IFN-λ1/IL29, IFN-λ2/interleukin (IL)-28A and IFN-λ3/IL-28B) consist of a recently identified group of IFNs, implicated initially in several human diseases, including cancer and autoimmunity. In this study, we sought to investigate the expression of type III IFNs and their common receptor IFN-λR1/IL-28Ra in Sjögren's syndrome (SS). Type III IFN expression was examined in minor salivary gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC) from SS patients and sicca-complaining controls. All type III IFN family members were detected in ductal and acinar epithelia of MSGs from both SS patients and sicca controls. IFN-λ2/IL-28A and IFN-λ3/IL-28B were also expressed in infiltrating mononuclear cells. In SS patients with intermediate MSG lesions, the epithelial expression of IFN-λ2/IL-28A was more intense compared to sicca controls (P < 0·05). The receptor IFN-λR1/IL-28Ra was detected in all types of cells except fibroblasts, and was exceptionally strong in plasmatocytoid dendritic cells, indicating that they are susceptible to type III IFN-mediated regulation. In the periphery, only IFN-λ1/IL-29 was detected in the sera and was elevated significantly in SS patients with intermediate MSG inflammatory lesions compared to sicca controls (P = 0·0053). None of the type III IFNs was expressed constitutively in resting SGECs; they were all induced readily by TLR-3 stimulation, suggesting that the in-situ epithelial expression can be attributed to local microenvironment. Type III IFNs are expressed in MSGs in a similar pattern to type I IFNs and their expression is probably subjected to micro-environmental regulation, suggesting that they are implicated in the inflammatory processes occurring in the affected exocrine glands.
26525510 Myricetin ameliorates the symptoms of collagen-induced arthritis in mice by inhibiting cat 2015 Myricetin, a common dietary flavonoid, is widely distributed in fruits and vegetables. It is known to be a food supplement contributing to human health because of its immune modulatory function, and its antioxidation, antitumor, and anti-inflammatory properties. In the present study, myricetin was shown to directly inhibit cathepsin K activity, a highly potent collagenase, which is the predominant papain-like cysteine protease expressed in osteoclasts and synovial fibroblasts. It was shown that the IC50 of myricetin for the recombinant human cathepsin was 585.3 µmol/L. Also, myricetin proved to have positive effects in murine collagen-induced arthritis (CIA). Mice suffering from CIA received a daily dose of myricetin (25 mg/kg, per os). During the study, the clinical severity of the CIA and the histopathology were evaluated. Biomarkers related to the histological evaluation of cartilage degradation, namely deoxypyridinoline, cartilage oligomeric matrix protein and C-terminal telopeptide degradation product of type I collagen (CTX-I), were analyzed. Myricetin treatment reduced the levels of biomarkers indicative of cartilage degradation (p < 0.05) and ameliorated the symptoms of CIA in mice at the clinical level (p < 0.01). As the inhibitory effect of myricetin on cathepsin K activity induced beneficial effects on CIA in mice, further investigation of therapeutic interventions with myricetin in other mammals or in human rheumatoid arthritis is recommended.