상산의 $NF-{\kappa}B$ 활성억제작용과 $IKK{\gamma}$의 연관성 연구

Relationship of Inhibitory Effects of Dichroa febrifuga and $IKK{\gamma}$ on the Activation of $NF-{\kappa}B$

Activation of $NF-{\kappa}B$ is known to be a trigger of various cellular disorders including inflammatory and autoimmune diseases such as rheumatoid arthritis. Numerous approaches are ongoing within laboratories to identify potential therapeutic agents which inhibit the $NF-{\kappa}B$ activation. In this study, we have tested the inhibitory effects of five traditional medicines on the activation of $NF-{\kappa}B$ by NIK. Among three medicines which exhibited inhibitory effect on the expression of $NF-{\kappa}B$ repoter plasmid, we investigated further the inhibitory mechanism of Dichroa febrifuga in connection with IKKY activity. Wild type $IKK{\gamma}$ inhibited the $NF-{\kappa}B$ activation by NIK but the C-terminal deletion mutant of IKKY did not show the inhibitory effect, indicating that the C-terminal leucine zipper domain of $NF-{\kappa}B$ is important for the inhibition of $NF-{\kappa}B$ activation. The water extract of Dichroa febrifuga(DFE) also strongly inhibited the $NF-{\kappa}B$ activation by NIK. The inhibitory activity of DFE appeared to be independent of the expression of $IKK{\gamma}$, suggesting that the pathways of inhibition by Dichroa febrifuga and $IKK{\gamma}$ are different. Our results suggest that Dichroa febrifuga can be used as a medicine for inhibition of the $NF-{\kappa}B$ activation in a wide range of cells without relation to the expression of $IKK{\gamma}$.