Transcriptional microarray analysis reveals suppression of histamine signaling by Kujin alleviates allergic symptoms through down-regulation of FAT10 expression

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 H1-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.

► TDI induced FAT10 mRNA elevation and Kujin extract suppressed this. ► Treatment with H1-antihistamines suppressed the TDI-induced FAT10 mRNA expression. ► Administration of histamine into the nasal cavity of rats induced FAT10 mRNA elevation. ► Anti-allergic action of Kujin is mediated by NF-κB inhibition through FAT10 gene down-regulation.