Quercetin regulates the inhibitory effect of monoclonal non-specific suppressor factor beta on tumor necrosis factor-alpha production in LPS-stimulated macrophages |
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Authors: | Nakamura Morihiko Omura Satomi |
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Institution: | Department of Cooperative Medical Research, Collaboration Center, Shimane University, Izumo, Japan. nkmr0515@med.shimane-u.ac.jp |
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Abstract: | Monoclonal non-specific suppressor factor beta (MNSFbeta) is a member of the ubiquitin-like family that has been implicated in various biological functions. Previous studies have demonstrated that MNSFbeta 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 MNSFbeta on TNFalpha production in LPS-stimulated Raw264.7 cells. Quercetin inhibited MNSFbeta siRNA-mediated enhancement of both TNFalpha production and ERK1/2 phosphorylation in LPS-stimulated Raw264.7 cells. Quercetin decreased the expression of 33.5-kDa MNSFbeta 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, MNSFbeta 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. |
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