Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) is characterized by hyperplastic synovial pannus tissue, which mediates destruction of cartilage and bone. Fibroblast-like synoviocytes (FLS) are a key component of the invasive pannus and have a major role in the initiation and perpetuation of destructive joint inflammation. NecroX-7 is a small chemical compound that exhibits cytoprotective effects and anti-oxidant activity. We investigated the inhibitory effects of NecroX-7 on the aggressiveness of TNF-α stimulated RA-FLS.
Methods: RA-FLS were cultured from synovial specimens obtained from RA patients undergoing joint replacement therapy. The cell viability was determined using CCK-8 colorimetric assay. The wound healing and transwell migration assay were performed to evaluate the effects of NecroX-7 on the migration of RA-FLS. Intracellular reactive oxygen species (ROS) generation was assessed by fluorometric assay. Matrix metalloproteinase-2 (MMP-2) and MMP-9 activity was measured using gelatin zymography. The expression of p-ERK1/2, p-p38, p-JNK and p-IκB was detected by Western blot analysis. The location of NF-κB p65 in RA-FLS was detected by immunofluorescence microscope.
Results: NecroX-7 had no significant cytotoxicity and inhibited migration of RA-FLS activated by TNF-α in vitro. NecroX-7 suppressed TNF-α-induced NF-κB activation by inhibiting ERK1/2 phosphorylation and IκB degradation and it prevented the nuclear translocation of NF-κB p65 with subsequent decrease in synthesis of MMP-2 and MMP-9. NecroX-7 reduced the generation of intracellular ROS (hydrogen peroxide, mitochondrial superoxide, cytosolic superoxide and peroxynitrite) in TNF-α-treated RA-FLS.
Conclusion: NecroX-7 reduces activities of MMP-2 and MMP-9 via inhibition of NF-κB signaling pathway and intracellular ROS formation in activated RA-FLS, suggesting that NecroX-7 might suppress the aggressiveness of RA-FLS in vivo. NecroX-7 may provide a new therapeutic option in treatment of RA.
To cite this abstract in AMA style:Yoo HJ, Park JK, Lee EY, Lee EB, Song YW. Necrox-7 Inhibits Cell Aggressiveness By Suppressing of NF-Kappa B Activation and Reactive Oxygen Species Generation in Human Rheumatoid Arthritis Fibroblast-like Synoviocytes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/necrox-7-inhibits-cell-aggressiveness-by-suppressing-of-nf-kappa-b-activation-and-reactive-oxygen-species-generation-in-human-rheumatoid-arthritis-fibroblast-like-synoviocytes/. Accessed October 27, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/necrox-7-inhibits-cell-aggressiveness-by-suppressing-of-nf-kappa-b-activation-and-reactive-oxygen-species-generation-in-human-rheumatoid-arthritis-fibroblast-like-synoviocytes/