RRC ID 42471
著者 Kim SJ, Shin HH, Park SY, Lee DS, Lee EA, Cho SD, Cho HR, Miyazawa K, Choi HS.
タイトル Induction of MMP-13 expression by soluble human glucocorticoid-induced tumor necrosis factor receptor in fibroblast-like synovial cells.
ジャーナル Osteoarthritis Cartilage
Abstract OBJECTIVE:We tested the hypothesis that human glucocorticoid-induced tumor necrosis factor receptor (hGITR/TR11) expressed on the surface of activated CD4(+) T cells is responsible for up-regulating the production of matrix metalloproteinase (MMP)-13 by fibroblast-like synoviocytes (FLSs).
METHODS:The level of MMP-13 was measured by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). Expressions of hGITR ligand (hGITRL) on the surface of FLSs and hGITR on the surface of human CD4(+) T cells were analyzed by flow cytometry and RT-PCR. Neutralizing antibodies (Abs) were used to block hGITRL and hGITR on the surface of FLSs and human CD4(+) T cells, respectively. Human CD4(+) T cells were cocultured with FLSs to facilitate interaction between hGITR on CD4(+) T cells and hGITRL on FLSs.
RESULTS:Soluble hGITR (shGITR) stimulated FLSs to produce MMP-13, and blockade of hGITRL reduced this effect. Direct contact between activated CD4(+) T and FLSs also induced the production of MMP-13, and neutralization of hGITR on activated CD4(+) T cells during coculture decreased the amount of MMP-13 produced by FLSs.
CONCLUSION:shGITR stimulated FLSs to produce MMP-13 via a signal through hGITRL. Direct contact between activated CD4(+) T cells and FLSs facilitated hGITR-hGITRL interaction, and resulted in inducing MMP-13. This effect may increase tissue destruction in chronic inflammation such as rheumatoid arthritis (RA).
巻・号 14(2)
ページ 146-53
公開日 2006-2-1
DOI 10.1016/j.joca.2005.08.012
PII S1063-4584(05)00239-6
PMID 16242974
MeSH Arthritis / enzymology* Arthritis, Rheumatoid / enzymology Arthritis, Rheumatoid / immunology Cell Line Chronic Disease Coculture Techniques Collagenases / analysis Collagenases / metabolism* Enzyme Induction Fibroblasts / enzymology* Fibroblasts / immunology Flow Cytometry Glucocorticoid-Induced TNFR-Related Protein Humans Immunoblotting Ligands Matrix Metalloproteinase 13 Osteoarthritis / enzymology Osteoarthritis / immunology RNA, Messenger / analysis Receptors, Nerve Growth Factor / metabolism* Receptors, Tumor Necrosis Factor / metabolism* Reverse Transcriptase Polymerase Chain Reaction Synovial Membrane / enzymology* Synovial Membrane / immunology T-Lymphocytes / metabolism Up-Regulation
IF 4.793
引用数 7
WOS 分野 ORTHOPEDICS RHEUMATOLOGY
リソース情報
ヒト・動物細胞 MH7A(RCB1512)