ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2710

Necrox-7 Inhibits Cell Aggressiveness By Suppressing of NF-Kappa B Activation and Reactive Oxygen Species Generation in Human Rheumatoid Arthritis Fibroblast-like Synoviocytes

Hyun Jung Yoo1,2, Jin Kyun Park2, Eun Young Lee2, Eun Bong Lee2 and Yeong Wook Song2,3, 1Department of Molecular Medicine and Biopharmaceutical Sciences, BK21 plus Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, South Korea, 2Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, 3Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine Seoul National University, Seoul, South Korea

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , , , ,

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster III

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.

Disclosure: H. J. Yoo, None; J. K. Park, None; E. Y. Lee, None; E. B. Lee, None; Y. W. Song, None.

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 .

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