RRC ID 42108
著者 Setoguchi K, Misaki Y, Kawahata K, Shimada K, Juji T, Tanaka S, Oda H, Shukunami C, Nishizaki Y, Hiraki Y, Yamamoto K.
タイトル Suppression of T cell responses by chondromodulin I, a cartilage-derived angiogenesis inhibitory factor: therapeutic potential in rheumatoid arthritis.
ジャーナル Arthritis Rheum
Abstract OBJECTIVE:Chondromodulin I (ChM-I), a cartilage matrix protein, promotes the growth and proteoglycan synthesis of chondrocytes. However, it also inhibits angiogenesis. Since ChM-I is expressed not only in cartilage, but also in the thymus, we investigated the modulation of T cell function by ChM-I to assess its therapeutic potential in rheumatoid arthritis (RA).
METHODS:The localization of ChM-I expression in mouse thymus tissue was examined by in situ hybridization. The proliferative response of peripheral blood T cells and synovial cells obtained from patients with RA was evaluated by (3)H-thymidine incorporation assay. The effects of ChM-I were examined using recombinant human ChM-I (rHuChM-I). Modulation of the antigen-specific immune response was evaluated by the recall response of splenic T cells and the delayed-type hypersensitivity response induced in the ear of mice primed with ovalbumin (OVA). Antigen-induced arthritis (AIA) was induced in mice by injecting methylated bovine serum albumin into the ankle joints 2 weeks after the priming.
RESULTS:ChM-I was expressed in the cortex of the thymus. Recombinant human ChM-I suppressed the proliferative response of mouse splenic T cells and human peripheral blood T cells stimulated with anti-CD3/CD28 antibodies, in a dose-dependent manner. Production of interleukin-2 was decreased in rHuChM-I-treated mouse CD4 T cells. Ten micrograms of rHuChM-I injected intraperitoneally into OVA-primed mice suppressed the induction of the antigen-specific immune response. Finally, rHuChM-I suppressed the development of AIA, and also suppressed the proliferation of synovial cells prepared from the joints of patients with RA.
CONCLUSION:These results suggest that ChM-I suppresses T cell responses and synovial cell proliferation, implying that this cartilage matrix protein has a therapeutic potential in RA.
巻・号 50(3)
ページ 828-39
公開日 2004-3-1
DOI 10.1002/art.20193
PMID 15022325
MeSH Adjuvants, Immunologic Angiogenesis Inhibitors / isolation & purification* Angiogenesis Inhibitors / metabolism Angiogenesis Inhibitors / pharmacology* Animals Antibody Formation Antigens / immunology Arthritis, Experimental / chemically induced Arthritis, Experimental / immunology Arthritis, Experimental / prevention & control Arthritis, Rheumatoid / drug therapy Cartilage / chemistry* Cell Division / drug effects Cell Line Collagen Epitopes Humans Intercellular Signaling Peptides and Proteins / isolation & purification* Intercellular Signaling Peptides and Proteins / metabolism Intercellular Signaling Peptides and Proteins / pharmacology* Membrane Proteins / isolation & purification* Membrane Proteins / metabolism Membrane Proteins / pharmacology* Mice Mice, Inbred BALB C Mice, Inbred DBA Recombinant Proteins / pharmacology Serum Albumin, Bovine Synovial Membrane / pathology T-Lymphocytes / cytology* Thymus Gland / metabolism Time Factors Tissue Distribution
引用数 15
WOS 分野 RHEUMATOLOGY
リソース情報
ヒト・動物細胞 Jurkat(RCB0806)