TY - JOUR
T1 - Auranofin inhibits overproduction of pro-inflammatory cytokines, cyclooxygenase expression and PGE2 production in macrophages
AU - Han, Shinha
AU - Kim, Kwanghee
AU - Kim, Hyunyul
AU - Kwon, Jeunghak
AU - Lee, Young Hee
AU - Lee, Chong Kil
AU - Song, Youngcheon
AU - Lee, Sang Jin
AU - Ha, Namjoo
AU - Kim, Kyungjae
N1 - Funding Information:
This work was supported by the Sahmyook University Research Found in 2006.
PY - 2008/1
Y1 - 2008/1
N2 - 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-α (TNF-α), interleukin-1β (IL-1β) 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-α, IL-1β 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.
AB - 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-α (TNF-α), interleukin-1β (IL-1β) 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-α, IL-1β 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.
KW - Anti-inflammation
KW - Auranofin
KW - Cyclooxygenase-2
KW - Nitric oxide
KW - Pro-inflammatory cytokines
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U2 - 10.1007/s12272-008-1122-9
DO - 10.1007/s12272-008-1122-9
M3 - Article
C2 - 18277610
AN - SCOPUS:40349116260
SN - 0253-6269
VL - 31
SP - 67
EP - 74
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
IS - 1
ER -