Quercetin Regulates the Inhibitory Effect of Monoclonal Non-Specific Suppressor Factor β on Tumor Necrosis Factor-α Production in LPS-Stimulated Macrophages

摘要

Monoclonal non-specific suppressor factor β (MNSFβ) is a member of the ubiquitin-like family that has been implicated in various biological functions. Previous studies have demonstrated that MNSFβ regulates the ERK1/2-MAPK cascade in the macrophage cell line Raw 264.7. In this study, we found evidence that the flavonol quercetin regulates the effect of MNSFβ on TNFa production in LPS-stimulated Raw264.7 cells. Quercetin inhibited MNSFβ siRNA-mediated enhancement of both TNFα production and ERK1/2 phosphorylation in LPS-stimulated Raw264.7 cells. Quercetin decreased the expression of 33.5-kDa MNSFβ adduct, which is important to the regulation of ERK1/2 activity, in unstimulated Raw264.7 cells. The various flavonoids tested, including other flavonols, did not affect the formation of this adduct. Collectively, MNSFβ and quercetin might share a common pathway in regulating the ERK1/2 pathway in macrophages. This is the first report describing the involvement of flavonoids in the action of ubiquitin-like proteins.