Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease
| Autor: | Stefan K. Drexler, Gertraud Orend, Masahide Kashiwagi, Brian M. J. Foxwell, Nidhi Sofat, Kim S. Midwood, Anna M. Piccinini, Fionula M. Brennan, Annette Trebaul, Julia J. Inglis, Sandra Sacre, Emma Chan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
musculoskeletal diseases medicine.medical_treatment Inflammation General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Mice medicine Animals Humans Cells Cultured Toll-like receptor biology business.industry Arthritis Tenascin C Tenascin General Medicine musculoskeletal system medicine.disease Protein Structure Tertiary Toll-Like Receptor 4 Transplantation Cytokine Rheumatoid arthritis Myeloid Differentiation Factor 88 embryonic structures Immunology TLR4 biology.protein Cytokines medicine.symptom business |
| Popis: | Although there have been major advances in the treatment of rheumatoid arthritis with the advent of biological agents, the mechanisms that drive cytokine production and sustain disease chronicity remain unknown. Tenascin-C (encoded by Tnc) is an extracellular matrix glycoprotein specifically expressed at areas of inflammation and tissue damage in inflamed rheumatoid joints. Here we show that mice that do not express tenascin-C show rapid resolution of acute joint inflammation and are protected from erosive arthritis. Intra-articular injection of tenascin-C promotes joint inflammation in vivo in mice, and addition of exogenous tenascin-C induces cytokine synthesis in explant cultures from inflamed synovia of individuals with rheumatoid arthritis. Moreover, in human macrophages and fibroblasts from synovia of individuals with rheumatoid arthritis, tenascin-C induces synthesis of proinflammatory cytokines via activation of Toll-like receptor 4 (TLR4). Thus, we have identified tenascin-C as a novel endogenous activator of TLR4-mediated immunity that mediates persistent synovial inflammation and tissue destruction in arthritic joint disease. |
| Databáze: | OpenAIRE |
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