Induction of MMP-13 expression by soluble human glucocorticoid-induced tumor necrosis factor receptor in fibroblast-like synovial cells.
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.


CONCLUSIONS
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).
Kim
S J
SJ
University of Ulsan, Ulsan, Republic of Korea.
Shin
H H
HH
Park
S Y
SY
Lee
D S
DS
Lee
E A
EA
Cho
S D
SD
Cho
H R
HR
Miyazawa
K
K
Choi
H S
HS
D001168:Arthritis / Q000201:enzymology*; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology; D002460:Cell Line; D002908:Chronic Disease; D018920:Coculture Techniques; D017364:Collagenases / Q000032:analysis / Q000378:metabolism*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000201:enzymology* / Q000276:immunology; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D053509:Matrix Metalloproteinase 13; D010003:Osteoarthritis / Q000201:enzymology / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000201:enzymology* / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation
D053450:Glucocorticoid-Induced TNFR-Related Protein; D008024:Ligands; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13