Session Information
Date: Sunday, November 8, 2015
Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Notch signaling is known to regulate cell fate decision and differentiation during embryonic and post-natal development. I have been reported that a Notch ligand Delta-like 1 (DLL1) promoted osteoclastogenesis via Notch2 activation and DLL1 blockade in rheumatoid arthritis (RA) model mouse reduced the number of osteoclasts in the affected joints. This DLL1 blockade also suppressed the joint inflammation by suppressing the production of pro-inflammatory mediators such as IL-6, GM-CSF, and MMP-3. In arthritic mouse joint, DLL1 expressed on macrophages and stimulated Notch2 on fibroblast-like synoviocytes (FLS), which enhanced the production of IL-6 and MMP-3. In this study, the role of DLL1 on the production of pro-inflammatory mediators by RA FLS was evaluated.
Methods: The expression of Notch receptors and ligands on RA FLS was analyzed by flow cytometry. OA FLS was also analyzed. DLL1 expression was investigated by imunohistochemical analysis of synovial tissue. FLS were stimulated with anti-Notch2 monoclonal antibody or DLL1-transfected CHO cells and IL-6, GM-CSF, and MMP-3 in the supernatants were measured by ELISA.
Results: As similar to mouse joint cells, Notch2 was expressed on RA-derived FLS and DLL1 was expressed on macrophages in RA synovium but not on FLS. Meanwhile, little expression of Notch2 was detected on osteoarthritis-derived FLS. Activation of Notch2 on RA FLS enhanced the production of IL-6 and GM-CSF. DLL1 stimulation also enhanced the production of IL-6, GM-CSF, and MMP-3 by RA FLS.
Conclusion: These results suggest that DLL1 activates Notch2 on RA FLS and enhances the production of RA-related pro-inflammatory mediators similar to mouse FLS. Therefore, DLL1 blockade may be a novel strategy to treat RA by suppressing the production of pro-inflammatory mediators in the joint as well as osteoclastogenesis.
To cite this abstract in AMA style:
Sekine C. Delta-like 1 Enhances the Production of Pro-Inflammatory Mediators By Fibroblast-like Synoviocytes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/delta-like-1-enhances-the-production-of-pro-inflammatory-mediators-by-fibroblast-like-synoviocytes/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/delta-like-1-enhances-the-production-of-pro-inflammatory-mediators-by-fibroblast-like-synoviocytes/