1. Inhibition of TNF-α-mediated inflammatory responses by a benzodioxolylacetylamino-linked benzothiazole analog in human fibroblast-like synoviocytes
- Author
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Lee, Young-Rae, Jin, Guo Hua, Lee, Sang-Myeong, Park, Jin-Woo, Ryu, Jae-Ha, Jeon, Raok, and Park, Byung-Hyun
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INFLAMMATION prevention , *TUMOR necrosis factors , *FIBROBLASTS , *SYNOVIOMA , *RHEUMATOID arthritis treatment , *CYTOKINES , *CHEMOKINES , *METALLOPROTEINASES , *GENE expression , *ORGANOSULFUR compounds , *NF-kappa B - Abstract
Abstract: The pathologic processes of rheumatoid arthritis are mediated by a number of cytokines, chemokines, and matrix metalloproteinases, the expressions of which are controlled by NF-κB. This study was performed to explore the effects of a benzothiazole analog, SPA0537, on the control of the NF-κB activation pathway. We also investigated whether SPA0537 had any anti-inflammatory effects in human rheumatoid fibroblast-like synoviocytes (FLS). SPA0537 inhibited the nuclear translocation and the DNA binding of NF-κB subunits, which correlated with the inhibitory effects on IKK phosphorylation and IκBα degradation in TNF-α-stimulated rheumatoid FLS. These events further suppressed chemokine production, matrix metalloproteinase secretion, and TNF-α-induced cell proliferation. In addition, SPA0537 inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor (MCSF) and receptor activator of the NF-κB ligand (RANKL) in bone marrow macrophages. These findings suggest that SPA0537 exerts anti-inflammatory effects in rheumatoid FLS through the inhibition of the NF-κB pathway. Therefore, it may have therapeutic value for the treatment of rheumatoid arthritis. [Copyright &y& Elsevier]
- Published
- 2011
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