Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Kim, S.J. et al.

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. 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).[1]

References

Induction of MMP-13 expression by soluble human glucocorticoid-induced tumor necrosis factor receptor in fibroblast-like synovial cells. Kim, S.J., Shin, H.H., Park, S.Y., Lee, D.S., Lee, E.A., Cho, S.D., Cho, H.R., Miyazawa, K., Choi, H.S. Osteoarthr. Cartil. (2006) [Pubmed]

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