Auranofin inhibits overproduction of pro-inflammatory cytokines, cyclooxygenase expression and PGE2 production in macrophages.
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.
Han
Shinha
S
Department of Pharmacy, Sahmyook University, Nowon-gu, Seoul 139-743, Korea.
Kim
Kwanghee
K
Kim
Hyunyul
H
Kwon
Jeunghak
J
Lee
Young-Hee
YH
Lee
Chong-Kil
CK
Song
Youngcheon
Y
Lee
Sang-Jin
SJ
Ha
Namjoo
N
Kim
Kyungjae
K
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
D018501:Antirheumatic Agents; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D001310:Auranofin; D012313:RNA; D015232:Dinoprostone