title: Scoparone inhibits PMA-induced IL-8 and MCP-1 production through suppression of NF-kappaB activation in U937 cells.
abstract: Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In this study, the effects of scoparone on the expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) and activation of nuclear factor-kappaB (NF-kappaB) were examined in U937 human monocytes activated with phorbol 12-myristate 13-acetate (PMA). Scoparone (5-100 microM) had no cytotoxic effect in unstimulated cells and concentration-dependently reversed PMA-induced toxicity in the cells stimulated with PMA. Scoparone concentration-dependently reduced the release of IL-8 and MCP-1 protein and expression of IL-8 and MCP-1 mRNA levels induced by PMA. Moreover, scoparone inhibited the levels of NF-kappaB-DNA complex and NF-kappaB activity in the cells stimulated with PMA in a concentration-dependent manner. Scoparone dose-dependently inhibited the phosphorylation of IkappaBalpha and nuclear translocation of NF-kappaB1 p50, RelA p65, and c-Rel p75. These data suggest that scoparone may inhibit the expression of chemokines (IL-8 and MCP-1) in PMA-stimulated U937 cells and a potential mechanism of scoparone may be inhibition of NF-kappaB activation, which is linked to inhibition of NF-kappaB subunits (NF-kappaB1 p50, RelA p65, and c-Rel p75) translocation via suppression of IkappaBalpha phosphorylation.
authors.affiliation: Department of Skin and Beauty, Seojeong College, Yangju 482-860, South Korea.
authors.forename: Seon Il
authors.initials: SI
authors.lastname: Jang
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jeong-Chi
authors.initials: JC
authors.lastname: Lee
authors.forename: Hong-Yong
authors.initials: HY
authors.lastname: Kim
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Young-Gab
authors.initials: YG
authors.lastname: Yun
authors.forename: Hyeon-Hee
authors.initials: HH
authors.lastname: Yu
authors.forename: Yong-Ouk
authors.initials: YO
authors.lastname: You
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003374:Coumarins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003374:Coumarins; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; C018145:scoparone; D013755:Tetradecanoylphorbol Acetate