title: Auranofin inhibits overproduction of pro-inflammatory cytokines, cyclooxygenase expression and PGE2 production in macrophages.
abstract: Auranofin (AF), a gold compound, is an orally active therapeutic agent used to treat rheumatoid arthritis (RA), a self-perpetuating inflammatory disease. RA is characterized by autoimmune-mediated proliferation of synovial cells that leads to inflammation, pain, and swelling in most major joints: However, the mechanism as to how AF relieves RA symptoms has not been fully elucidated. The object of this study was to examine the ability of AF to immunomodulate macrophages as antigen presenting cells (APCs). Macrophages are recognized as playing an important role in the pathogenesis of RA, in that there is a relative abundance of macrophage-derived cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in rheumatoid synovium. In this work, we tested whether AF (2.5-20 mM) could inhibit inflammatory activity in the macrophage cell line RAW 264.7. AF decreased production of nitric oxide (NO) and the pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6 in macrophages. Furthermore, AF inhibited cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production in a concentration-dependent manner. In conclusion, these findings may provide an explanation for the clinical effects of AF in patients with RA.
authors.affiliation: Department of Pharmacy, Sahmyook University, Nowon-gu, Seoul 139-743, Korea.
authors.forename: Shinha
authors.initials: S
authors.lastname: Han
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Kim
authors.forename: Hyunyul
authors.initials: H
authors.lastname: Kim
authors.forename: Jeunghak
authors.initials: J
authors.lastname: Kwon
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
authors.forename: Youngcheon
authors.initials: Y
authors.lastname: Song
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Namjoo
authors.initials: N
authors.lastname: Ha
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Kim
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018501:Antirheumatic Agents; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D001310:Auranofin; D012313:RNA; D015232:Dinoprostone