Ichikawa, Kimihisa and Liu, Weimin and Fleck, Martin and Zhang, Huangge and Zhao, Limin and Ohtsuka, Toshiaki and Wang, Zheng and Liu, Di and Mountz, John D. and Ohtsuki, Masahiko and Koopman, William J. and Kimberly, Robert and Zhou, Tong (2003) TRAIL-R2 (DR5) mediates apoptosis of synovial fibroblasts in rheumatoid arthritis. JOURNAL OF IMMUNOLOGY, 171 (2). pp. 1061-1069. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
TRAIL has been proposed as an anti-inflammatory cytokine in animal models of rheumatoid arthritis (RA). Using two agonistic mAbs specific for TRAIL-R1 (DR4) and TRAIL-R2 (DR5), we examined the expression and function of these death receptors in RA synovial fibroblast cells. The synovial tissues and primary synovial fibroblast cells isolated from patients with RA, but not those isolated from patients with osteoarthritis, selectively expressed high levels of cell surface DR5 and were highly susceptible to anti-DR5 Ab (TRA-8)-mediated apoptosis. In contrast, RA synoviocytes did not show increased expression of TRAIL-R1 (DR4), nor was there any difference in expression of Fas between RA and osteoarthritis synovial cells. In vitro TRA-8 induced apoptosis of RA synovial cells and inhibited production of matrix metalloproteinases induced by pro-inflammatory cytokines. In vivo TRA-8 effectively inhibited hypercellularity of a SV40-transformed RA synovial cell line and completely prevented bone erosion and cartilage destruction induced by these cells. These results indicate that increased DR5 expression and susceptibility to DR5-mediated apoptosis are characteristic of the proliferating synovial cells in RA. As highly proliferative transformed-appearing RA synovial cells play a crucial role in bone erosion and cartilage destruction in RA, the specific targeting of DR5 on RA synovial cells with an agonistic anti-DR5 Ab may be a potential therapy for RA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLLAGEN-INDUCED ARTHRITIS; CYTOTOXIC LIGAND TRAIL; ANTI-FAS ANTIBODY; MONOCLONAL-ANTIBODIES; DECOY RECEPTOR; DEATH DOMAIN; MICE; EXPRESSION; ONCOGENES; FAMILY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Sep 2021 08:49 |
| Last Modified: | 06 Sep 2021 08:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38819 |
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