Session Title: Rheumatoid Arthritis - Animal Models
Session Type: Abstract Submissions (ACR)
TSAHC, a toluenesulfonylamido-chalcone, 4-(p-toluenesulfonylamido)-4-hydroxychalcone is a compound to block proliferation and metastatic potential of cancer cells. Fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS) have inflammatory phenotypes and tumor-like characteristics such as abnormal proliferation, apoptotic resistance, migration, and invasion. Thus, this study was performed to determine whether TSAHC suppress inflammation and joint destruction in K/BxN serum transfer arthritic mice and RA-FLS.
TSAHC was synthesized with a purity > 99.0%. Treatment included intravenous injections of PBS, vehicle, or TSAHC (5mg/kg once every other day, n=9-10 for each group) for 10 days in K/BxN serum transfer model. Arthritis severity and ankle histology was evaluated using a semi-quantitative scoring system. The levels of inflammatory cytokines in the joints and serum were measured by ELISA and quantitative PCR. The NF-kB activation and cytokine expression were assessed by Western blotting and quantitative PCR using RA-FLS.
The mice injected with TSAHC showed less severe arthritis than vehicle group in clinical score (5.4 ± 0.39 vs. 3.9 ± 0.79, mean ± SE, p < 0.05) and the change of ankle thickness (0.49 ± 0.04 vs. 0.29 ± 0.04 mm, p < 0.01). The pathologic analysis also showed decreased inflammation and bone erosion in TSAHC group. The levels of TNF-α, IL1-β, and sRANKL were decreased in serum and ankle tissue of TSAHC group than vehicle. In addition, IL-10 was increased nearly by 51% in TSAHC group than vehicle (p
This study indicates that TSAHC inhibit inflammation and bone destruction in arthritic mice and decrease IL- 6 production in RA-FLS via inhibition of NF-κB activation. Therefore, TSAHC may have therapeutic potential for the treatment of RA.
Y. H. Cheon,
W. H. Yoo,
Y. S. Suh,
M. G. Jeon,
H. O. Kim,
S. I. Lee,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/toluenesulfonylamido-chalcone-4-p-toluenesulfonylamido-4-hydroxychalcone-tsahc-suppresses-inflammatory-response-and-joint-destruction-in-an-experimental-arthritic-mice-and-fibroblast-like-synovio/