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KMID : 0613820100200121772
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Journal of Life Science
2010 Volume.20 No. 12 p.1772 ~ p.1776
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Auranofin Downregulates Nuclear Factor-κB Activation via Nrf2-Independent Mechanism
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Kim Nam-Hoon
Park Hyo-Jung
Kim In-Sook
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Abstract
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Transcription factors Nrf2 and NF-κB are important regulators of the innate immune response, and their cross-talks in inflammation have been reported. Previously, we demonstrated that gold(I)-compound auranofin, an inhibitor of NF-κB signal, induced Nrf2 activation in human synovial cells and monocytic cells. To investigate whether the Nrf2 activation is involved in the mechanism of the auranofin- attenuated NF-κB signaling, we examined the effects of Nrf2 knockdown on NF-κB activation using rheumatic synovial cells. When the cells were transfected with a specific siRNA for Nrf2, the gene expression was perfectly blocked. However, the Nrf2 knockdown did not cancel the suppressive effect of auranofin on TNF-α-induced IκB-α degradation. Treatment with a specific siRNA for HO-1, which is a target of Nrf2 and plays a role in anti-inflammation, also did not affect the blocking activity of auranofin on IκB-α degradation. In addition, auranofin-inhibited ICAM-1 expression was not restored by Nrf2 knockdown. These findings indicate that the activated Nrf2 and HO-1 are not associated with the suppressive action of auranofin on the pro-inflammatory cytokines-stimulated NF-κB activation. This suggests that Nrf2/HO-1 and NF-κB signals, which are regulated by auranofin, participate in the anti-inflammatory action of auranofin via independent pathways in rheumatic synovial cells.
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KEYWORD
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Auranofin, nuclear factor-erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), nuclear factor-κB(NF-κB), intercellular adhesion molecule-1(ICAM-1)
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