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Published on: December 22, 2020
Cadherin-11 regulates fibroblast inflammation
Sook Kyung Chang1, Erika H Noss, Mei Chen
1Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Summary
Cadherin-11 (cad-11) engagement on fibroblasts triggers the release of inflammatory cytokines like IL-6, contributing to rheumatoid arthritis (RA). Targeting cad-11 may reduce inflammation by blocking this pathway.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- Fibroblasts contribute to inflammation by producing cytokines and chemokines.
- In rheumatoid arthritis (RA), synovial fibroblasts are key sources of IL-6 and RANKL.
- Previous studies showed targeting cadherin-11 (cad-11) reduced joint inflammation.
Purpose of the Study:
- To elucidate the mechanism by which anti-cad-11 antibodies reduce inflammation.
- To investigate the role of cad-11 engagement in inducing inflammatory cytokine production by synovial fibroblasts.
Main Methods:
- Investigated the effect of cad-11 engagement on IL-6 secretion from synovial fibroblasts.
- Examined the synergistic effects of cad-11 engagement with TNF-α and IL-1β.
- Analyzed cad-11 induced activation of MAP kinases and NF-κB.
- Compared IL-6 levels in cad-11 mutant mice versus wild-type mice with inflammatory arthritis.
Main Results:
- Cadherin-11 engagement induces synovial fibroblasts to secrete IL-6.
- Cad-11 engagement synergizes with TNF-α and IL-1β to enhance IL-6 production.
- Cad-11 activation of MAP kinases and NF-κB mediates IL-6 induction.
- Reduced IL-6 levels were observed in the inflamed joints of cad-11 mutant mice.
Conclusions:
- Cadherin-11 plays a significant role in modulating fibroblast-mediated inflammation.
- Targeting cad-11 may be a therapeutic strategy for inflammatory diseases like RA by inhibiting pro-inflammatory cytokine release.
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