دورية أكاديمية
Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C: Targeting fibronectin type III repeats of tenascin-C in rheumatoid arthritis.
| العنوان: | Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C: Targeting fibronectin type III repeats of tenascin-C in rheumatoid arthritis. |
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| المؤلفون: | Mehta BB; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Tiwari A; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Sharma S; Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Shukla A; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Sharma M; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Vasishta RK; Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Sen RK; Department of Orthopaedics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Sharma A; Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Luthra-Guptasarma M; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. Electronic address: guptasarma.manni@pgimer.edu.in. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2018 May; Vol. 58, pp. 15-23. Date of Electronic Publication: 2018 Mar 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Arthritis, Experimental/*therapy , Arthritis, Rheumatoid/*therapy , Fibroblasts/*physiology , Fibronectin Type III Domain/*immunology , Immunotherapy/*methods , Single-Chain Antibodies/*therapeutic use , Synovial Membrane/*pathology , Tenascin/*immunology, Animals ; Antibodies/immunology ; Arthritis, Experimental/immunology ; Arthritis, Rheumatoid/immunology ; Cell Adhesion/drug effects ; Cell Movement/drug effects ; Cells, Cultured ; Collagen/immunology ; Disease Models, Animal ; Fibrosis ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Targeted Therapy |
| مستخلص: | Tenascin-C (TN-C) levels are elevated in the synovial tissue and fluid, as well as cartilage of rheumatoid arthritis (RA) patients. In addition, the presence of TN-C fragments has also been documented in arthritic cartilage. We have previously shown that a single chain variable fragment antibody (TN64), directed against the fibronectin type III repeats 1-5 (TNfnIII 1-5) of TN-C, effectively inhibits fibrotic pathology. Given that fibrosis results from chronic inflammation, and the fact that increased levels of TN-C in the synovial fluid of patients with RA contributes to synovial inflammation and joint destruction, we aimed to investigate the role of TNfnIII 1-5 region of TN-C in RA pathogenesis. Using either the wild type or variants of the two integrin-binding motifs (RGD and AEIDGIEL) present within the TNfnIII 1-5 polypeptide, we demonstrate that the adhesion and migration of synovial fibroblasts is RGD-dependent. The antibody TN64 is effective in inhibiting migration of cells in response to TnfnIII 1-5, and prevents fibroblast-mediated destruction of cartilage. The TN64 antibody was further tested in collagen antibody induced arthritic (CAIA) mice. Our data shows the efficacy of TN64 in preventing induction of arthritis, with significant downregulation of RA-associated cytokines. This suggests that components of the extracellular matrix such as the TNfnIII 1-5 region of TN-C could be exploited to develop therapies to suppress inflammation seen in RA. The TN64 antibody is one such promising candidate in the development of novel treatments for RA. (Copyright © 2018 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Collagen antibody induced arthritis (CAIA); Extracellular matrix; Inflammation; Rheumatoid arthritis; Tenascin; scFv antibody |
| المشرفين على المادة: | 0 (Antibodies) 0 (Single-Chain Antibodies) 0 (Tenascin) 9007-34-5 (Collagen) |
| تواريخ الأحداث: | Date Created: 20180313 Date Completed: 20181022 Latest Revision: 20181022 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.intimp.2018.02.022 |
| PMID: | 29529488 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2018.02.022 |