著作: [水口 博之]/Nariai Y/Kato S/Nakano T/Kanayama T/[柏田 良樹]/[根本 尚夫]/[川添 和義]/[高石 喜久]/[北村 嘉章]/[武田 憲昭]/[福井 裕行]/Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes./[Pharmacology Research & Perspectives]
(英) Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes.
(英) Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)-4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin-derived antiallergic compound and investigate its mechanism of action. The H1R and IL-4 mRNA levels were determined by real-time quantitative RT-PCR. To investigate the effects of maackiain in vivo, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as a nasal hypersensitivity animal model. We identified (-)-maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL-4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (-)-Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ, which led to the suppression of H1R gene transcription. However, (-)-maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI-induced upregulations of H1R and IL-4 gene expressions in TDI-sensitized rats. These data suggest that (-)-maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI-sensitized allergy model rats through the inhibition of H1R and IL-4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation.
Pharmacology Research & Perspectives(British Pharmacological Society/American Society for Pharmacology and Experimental Therapeutics)
|年月日||必須||2015年 8月 10日|