Previously, we have shown that hot water extract from Kujin, the dried roots of Sophora flavescens alleviates allergic symptoms by suppressing histamine signaling at the transcription level in toluene 2,4-diisocyanate (TDI)-sensitized rats. To know more insights into the mechanism of the anti-allergic action of Kujin, we carried out the microarray analysis to explore genes that were up-regulated by treatment with TDI and also were suppressed these up-regulated gene expression by Kujin. Microarray analysis revealed the substantial up-regulation of FAT10 (also called UbD) mRNA due to TDI sensitization and Kujin extract significantly suppressed this up-regulation. FAT10 is an ubiquitin like protein having an active role in the immune system and is induced by proinflammatory cytokines. Activation of NF-κB by FAT10 also has been reported. However, the role of FAT10 in allergic pathogenesis remains unknown. Here we investigated the correlation of FAT10-NF-κB signaling with histamine signaling in TDI-sensitized rats. Real time RT-PCR analysis confirmed that treatment with TDI up-regulated FAT10 mRNA expression in the nasal mucosa of TDI-sensitized rats and Kujin extract suppressed this elevation. Treatment with H(1)-antihistamines suppressed the TDI-induced up-regulation of FAT10 mRNA expression in TDI-sensitized rats. Direct administration of histamine into the nasal cavity of non-TDI-treated normal rats up-regulated the expression of FAT10 mRNA. Our data suggest that Kujin might alleviate allergic symptoms by inhibition of NF-κB activation through suppression of histamine-induced up-regulation of FAT10 mRNA expression.
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