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Condition: Autoimmune Disease

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Total 230 results found since Jan 2013.

High-dose BAFF receptor specific mAb-siRNA conjugate generates Fas-expressing B cells in lymph nodes and high-affinity serum autoantibody in a myasthenia mouse model.
Abstract We investigated potential therapeutic effects of a conjugate of BAFF receptor specific- monoclonal antibody and short interference RNA in a mouse model of myasthenia gravis (EAMG). Whereas high-dose siRNA conjugate resulted in significant accumulation of Fas expressing CD19+/ B220+ cells and concurrent expression of type 1 interferon in lymph nodes, low-dose conjugate did not induce FAS expression but caused marked BAFF receptor deficiency in lymph nodes that was further associated with improved MG symptoms. Unexpectedly, despite inhibiting BAFF receptor significantly in PBMCs and secondary lymphoid organ...
Source: Clinical Immunology - January 14, 2017 Category: Allergy & Immunology Authors: Ibtehaj N, Anderson KE, Huda R Tags: Clin Immunol Source Type: research

Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes
Conclusions Inhibition of HDAC3 in RA FLS largely recapitulates the effects of pan-HDACi in suppressing inflammatory gene expression, including type I IFN production in RA FLS. Our results identify HDAC3 as a potential therapeutic target in the treatment of RA and type I IFN-driven autoimmune diseases.
Source: Annals of the Rheumatic Diseases - December 8, 2016 Category: Rheumatology Authors: Angiolilli, C., Kabala, P. A., Grabiec, A. M., Van Baarsen, I. M., Ferguson, B. S., Garcia, S., Malvar Fernandez, B., McKinsey, T. A., Tak, P. P., Fossati, G., Mascagni, P., Baeten, D. L., Reedquist, K. A. Tags: Open access Basic and translational research Source Type: research

The Fli-1 transcription factor is a critical regulator for controlling the expression of chemokine C-X-C motif ligand 2 (CXCL2)
In this study, we demonstrate that endothelial cells transfected with Fli-1 specific siRNA produce significantly less CXCL2 compared to cells transfected with control siRNA after stimulation by the Toll-like receptor (TLR) 4 ligands, lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α). The production of CXCL2 in endothelial cells stimulated with LPS stimulation is dose-dependent. We found that Fli-1 binds to the CXCL2 promoter as established by Chromatin immunoprecipitation‎ (ChIP) assay. Transient transfection assays show that Fli-1 drives transcription from the CXCL2 promoter in a dose-dependent manner an...
Source: Molecular Immunology - November 24, 2016 Category: Allergy & Immunology Source Type: research

Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis.
Abstract Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by in vivo electropor...
Source: The American Journal of Pathology - September 25, 2016 Category: Pathology Authors: Gomez AM, Stevens JA, Mané-Damas M, Molenaar P, Duimel H, Verheyen F, Cossins J, Beeson D, De Baets MH, Losen M, Martinez-Martinez P Tags: Am J Pathol Source Type: research

Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice
Conclusions/interpretation Epigenetic modification of DNA by methylation in response to immunological stressors may be a mechanism that affects insulin gene expression during the progression of type 1 diabetes.
Source: Diabetologia - April 9, 2016 Category: Endocrinology Source Type: research

Modified siRNA effectively silence inducible immunoproteasome subunits in NSO cells.
Abstract The pathogenesis of autoimmune and neurodegenerative diseases involves overexpression of inducible subunits of the immunoproteasome. However, the clinical application of inhibitors to inducible subunits of the immunoproteasome has been limited due to systemic toxicity. Here, we designed siRNAs that efficiently silence LMP2, LMP7 and MECL-1 gene expression. Inducible subunits of the immunoproteasome are complex siRNA targets because they have a long half-life; therefore, we introduced 2'-O-methyl modifications into nuclease-sensitive sites. This led to 90-95% silencing efficiency and prolonged silencing, e...
Source: Biochimie - March 1, 2016 Category: Biochemistry Authors: Gvozdeva OV, Belogurov AV, Kuzina ES, Gabibov AG, Meschaninova MI, Ven Yaminova AG, Zenkova MA, Vlassov VV, Chernolovskaya EL Tags: Biochimie Source Type: research

MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes
Conclusion Taken together, these results indicate that miR-20a may play a pivotal role in the NLRP3-inflammasome by targeted inhibit TXNIP expression in AA FLSs.
Source: Joint Bone Spine - February 29, 2016 Category: Orthopaedics Source Type: research

Inhibition of B lymphocyte-induced maturation protein-1 reduces the production of autoantibody and alleviates symptoms of systemic lupus erythematosus.
This study aimed to investigate the role of Blimp-1 in the development of SLE and autoimmune-like symptoms. Lentivirus-mediated Blimp-1 siRNA was constructed and injected into MRL-Fas(lpr) lupus mice. The expression levels of Blimp-1, J-chain, C-myc, XBP-1 and BCMA in peripheral blood mononuclear cells (PMBCs) were determined by RT-PCR. Anti-dsDNA autoantibody levels were detected using ELISA. The expression levels of Blimp-1 in liver, kidney, spleen and lymph nodes of mice were also detected by Western blot. The 24-h urinary protein was monitored weekly. Our results demonstrated that in MRL-Fas(lpr) lupus mice, Blimp-1 wa...
Source: Autoimmunity - February 17, 2016 Category: Allergy & Immunology Tags: Autoimmunity Source Type: research

A novel role for RGMa in modulation of bone marrow-derived dendritic cells maturation induced by lipopolysaccharide.
Abstract Repulsive guidance molecule a (RGMa) is known to mediate immune responses and has been indicated to modulates T cell activation and autoimmune diseases by dendritic cells (DCs), which hints its significant function in the latter cells. The aim of our study, therefore, was to evaluate the function of RGMa in DC maturation. We found that small interfering RNA (siRNA) successfully silenced the expression of RGMa in DCs. Even after LPS stimulation, RGMa-silenced DCs displayed an immature morphology, characterized by small, round cells with a few cell processes and organelles, and many pinocytotic vesicles. In...
Source: International Immunopharmacology - February 17, 2016 Category: Allergy & Immunology Authors: Xu X, Gao Y, Shan F, Feng J Tags: Int Immunopharmacol Source Type: research

TNF-α induces vascular endothelial cells apoptosis through overexpressing pregnancy induced noncoding RNA in Kawasaki disease model.
In this study, firstly we verified the overexpressed TNF-α in KD patients, and found TNF-α was able to induce HUVECs apoptosis and inhibit HUVECs proliferation. After this we screened out pregnancy induced noncoding RNA (PINC) was significantly overexpression in TNF-α treated HUVECs. We also found PINC overexpressed in KD patients. For further study, we designed two siRNA of PINC. After silenced the expression of PINC in HUVECs, we found the Knockdown of PINC enhanced the viability of HUVECs treated with TNF-α, and increased the expression of anti-apoptotic and reduced the expression of apoptotic gene. These results su...
Source: The International Journal of Biochemistry and Cell Biology - January 18, 2016 Category: Biochemistry Authors: Jiang C, Fang X, Jiang Y, Shen F, Hu Z, Li X, Huang X Tags: Int J Biochem Cell Biol Source Type: research

Downstream activation of NF-κB in the EDA-A1/EDAR signalling in Sjögren's syndrome and its regulation by the ubiquitin-editing enzyme A20.
This article is protected by copyright. All rights reserved. PMID: 26724675 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - January 2, 2016 Category: Allergy & Immunology Authors: Sisto M, Barca A, Lofrumento DD, Lisi S Tags: Clin Exp Immunol Source Type: research

Histone methylation and STAT3 differentially regulate IL‐6‐induced MMP gene activation in rheumatoid arthritis synovial fibroblasts
Conclusion. We show that the histone methylation and STAT3 regulate spontaneous and IL‐6‐induced MMPs gene activation in RASFs. The network of the chromatin structure and transcription factors may regulate distinct arthritogenic properties of RASFs. This article is protected by copyright. All rights reserved.
Source: Arthritis and Rheumatism - December 29, 2015 Category: Rheumatology Authors: Yasuto Araki, Takuma Tsuzuki Wada, Yoshimi Aizaki, Kojiro Sato, Kazuhiro Yokota, Kenta Fujimoto, Yoon‐Taek Kim, Hiromi Oda, Riki Kurokawa, Toshihide Mimura Tags: Full Length Source Type: research

DCIR negatively regulates CpG-ODN-induced IL-1β and IL-6 production
In this study, we demonstrate that CpG-ODN stimulation can promote DCIR expression in macrophages and DCIR triggering inhibits the production of CpG-ODN-induced proinflammatory cytokines. We further confirm that siRNA-mediated knockdown of DCIR expression enhances CpG-ODN-induced phosphorylation of Erk1/2, JNK1/2 and p38 in macrophages. Collectively, these results indicate that DCIR is a negatively regulator in TLR9-mediated innate immune response.
Source: Molecular Immunology - October 26, 2015 Category: Allergy & Immunology Source Type: research

Role of TRIF Small Interference RNA (siRNA) in Chronic Experimental Allergic Encephalomyelitis (EAE).
CONCLUSIONS The expression of TRIF can be down-regulated by siRNA, thereby alleviating the severity of EAE via its inhibition of interleukin and cytokine release. This may provide new insights for future treatment of MS. PMID: 26324415 [PubMed - in process]
Source: Medical Science Monitor - September 4, 2015 Category: Research Tags: Med Sci Monit Source Type: research

Inhibition of G-Protein βγ Signaling Decreases Levels of Messenger RNAs Encoding Proinflammatory Cytokines in T Cell Receptor-Stimulated CD4+ T Helper Cells
Conclusions: Inhibiting Gβγ to produce these shifts in cytokine mRNA production might be beneficial for patients with autoimmune diseases such as rheumatoid arthritis (RA), Crohn’s disease (CD), psoriasis, multiple sclerosis (MS), and Hashimoto’s thyroiditis (HT), in which both IFN-γ and IL-17A are elevated. Published on None
Source: Journal of Molecular Signaling - August 21, 2015 Category: Molecular Biology Source Type: research