4 research outputs found
Maackiain Suppresses H1R and IL-4 Gene Transcriptions
Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)ā4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujināderived antiallergic compound and investigate its mechanism of action. The H1R and ILā4 mRNA levels were determined by realātime quantitative RTāPCR. To investigate the effects of maackiain in vivo, tolueneā2,4ādiisocyanate (TDI)āsensitized rats were used as a nasal hypersensitivity animal model. We identified (ā)āmaackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of ILā4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (ā)āMaackiain inhibited of PKCĪ“ translocation to the Golgi and phosphorylation of Tyr311 on PKCĪ“, which led to the suppression of H1R gene transcription. However, (ā)āmaackiain did not show any antioxidant activity or inhibition of PKCĪ“ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDIāinduced upregulations of H1R and ILā4 gene expressions in TDIāsensitized rats. These data suggest that (ā)āmaackiain is a novel antiallergic compound that alleviates nasal symptoms in TDIāsensitized allergy model rats through the inhibition of H1R and ILā4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCĪ“ activation