Abstract | OBJECTIVE: METHODS: RESULTS:
DX-2400 treatment significantly reduced cartilage degradation and disease progression in mice with CIA. Importantly, when combined with TNF blockade, DX-2400 acted synergistically, inducing long-term benefit. DX-2400 also inhibited the up-regulation of interleukin-12 ( IL-12)/IL-23 p40 via polarization toward an M2 phenotype in bone marrow-derived macrophages. Increased production of IL-17 induced by anti-TNF, which correlated with an incomplete response to anti-TNF, was abrogated by combined treatment with DX-2400 in CIA. CONCLUSION: Targeting MT1-MMP provides a potential strategy for joint protection, and its combination with TNF blockade may be particularly beneficial in RA patients with an inadequate response to anti-TNF therapy.
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Authors | Kazuyo Kaneko, Richard O Williams, Daniel T Dransfield, Andrew E Nixon, Ann Sandison, Yoshifumi Itoh |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 68
Issue 2
Pg. 521-31
(Feb 2016)
ISSN: 2326-5205 [Electronic] United States |
PMID | 26315469
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- DX-2400
- IL10 protein, mouse
- Interleukin-12 Subunit p40
- Interleukin-17
- Lipopolysaccharides
- Matrix Metalloproteinase Inhibitors
- Mmp14 protein, mouse
- Tumor Necrosis Factor-alpha
- Interleukin-10
- Interferon-gamma
- Matrix Metalloproteinase 14
- Etanercept
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Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Antibodies, Monoclonal, Humanized
- Arthritis, Experimental
(immunology, pathology)
- Cartilage, Articular
(drug effects, pathology)
- Disease Progression
- Etanercept
(pharmacology)
- In Vitro Techniques
- Interferon-gamma
(drug effects, immunology)
- Interleukin-10
(immunology)
- Interleukin-12 Subunit p40
(drug effects, immunology)
- Interleukin-17
(immunology)
- Lipopolysaccharides
(pharmacology)
- Lymph Nodes
(drug effects, immunology, pathology)
- Macrophages
(drug effects, immunology)
- Matrix Metalloproteinase 14
(drug effects, immunology)
- Matrix Metalloproteinase Inhibitors
(pharmacology)
- Mice
- Mice, Inbred DBA
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
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