title: Inhibition of TNF-α-mediated inflammatory responses by a benzodioxolylacetylamino-linked benzothiazole analog in human fibroblast-like synoviocytes.
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.
authors.affiliation: Department of Biochemistry, Research Institute for Endocrine Sciences and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Jin
authors.forename: Sang-Myeong
authors.initials: SM
authors.lastname: Lee
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000083:Acetanilides / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D052160:Benzothiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010010:Osteoclasts / Q000187:drug effects; D012213:Rheumatic Fever / Q000188:drug therapy / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C559908:2-benzo(1,3)dioxol-5-yl-N-(2-(benzothiazol-4-yloxymethyl)phenyl)-N-benzylacetamide; D000083:Acetanilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052160:Benzothiazoles; D018836:Inflammation Mediators; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases