Abstract | OBJECTIVE: METHODS: Synovial tissue specimens from the joints of patients with rheumatoid arthritis (RA) and the joints of mice with collagen-induced arthritis (CIA) were examined for TREM-1 expression, using flow cytometric analysis. Expression of TREM-1 on macrophages was induced by lipopolysaccharide, with or without a cyclooxygenase inhibitor. Rheumatoid synovial cells were stimulated with agonistic anti-TREM-1 antibodies. Recombinant adenovirus encoding the extracellular domain of TREM-1 fused with IgG-Fc (AxCATREM-1 Ig) or synthetic TREM-1 antagonistic peptides were injected to treat CIA, and the clinical manifestations of the antigen-specific T cell and B cell responses were evaluated. RESULTS: TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with CIA. Unlike murine macrophages, human monocyte/macrophages did not depend on prostaglandin E2 for up-regulation of TREM-1. Agonistic anti-TREM-1 antibodies promoted tumor necrosis factor alpha production from rheumatoid synovial cells. Blockade of TREM-1 using AxCATREM-1 Ig and antagonistic peptides ameliorated CIA without affecting the serum levels of anti- type II collagen antibodies or the proliferative responses of splenocytes to type II collagen. CONCLUSION: TREM-1 ligation contributes to the pathology of autoimmune arthritis. The results of this study implied that blockade of TREM-1 could be a new approach to rheumatic diseases that is safer than the presently available immunosuppressive treatments.
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Authors | Yousuke Murakami, Tohru Akahoshi, Naoko Aoki, Masayasu Toyomoto, Nobuyuki Miyasaka, Hitoshi Kohsaka |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 60
Issue 6
Pg. 1615-23
(Jun 2009)
ISSN: 0004-3591 [Print] United States |
PMID | 19479878
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunoglobulin G
- Inflammation Mediators
- Membrane Glycoproteins
- Peptides
- Receptors, Immunologic
- TREM1 protein, human
- Triggering Receptor Expressed on Myeloid Cells-1
- Dinoprostone
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Topics |
- Animals
- Arthritis, Experimental
(drug therapy, metabolism)
- Arthritis, Rheumatoid
(drug therapy, metabolism)
- Autoimmune Diseases
(drug therapy, metabolism)
- Cells, Cultured
- Dinoprostone
(metabolism)
- Disease Models, Animal
- Humans
- Immunoglobulin G
(pharmacology)
- Inflammation Mediators
(antagonists & inhibitors, metabolism)
- Macrophages
(metabolism, pathology)
- Male
- Membrane Glycoproteins
(antagonists & inhibitors, metabolism)
- Mice
- Mice, Inbred DBA
- Peptides
(pharmacology)
- Receptors, Immunologic
(antagonists & inhibitors, metabolism)
- Synovial Membrane
(metabolism, pathology)
- Triggering Receptor Expressed on Myeloid Cells-1
- Up-Regulation
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