It has been reported that the
histamine H1 receptor (H1R) gene is up-regulated in patients with
allergic rhinitis and H1R expression level strongly correlates with the severity of
allergy symptoms. Accordingly compounds that suppress the H1R gene expression are promising as useful
anti-allergic medications. Recently, we demonstrated that
histamine or phorbol-12-myristate-13-acetate (PMA) stimulation induced the up-regulation of H1R gene expression through the
protein kinase Cδ (PKCδ)/
extracellular signal-regulated kinase/
poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells expressing H1R endogenously.
Quercetin is one of the well-characterized
flavonoids and it possesses many biological activities including
anti-allergic activity. However, effect of
quercetin on H1R signaling is remained unknown. In the present study, we examined the effect of
quercetin on
histamine- and PMA-induced up-regulation of H1R gene expression in HeLa cells. We also investigated its in vivo effects on the toluene-2,4-diisocyanate (TDI)-sensitized
allergy model rats.
Quercetin suppressed
histamine- and PMA-induced up-regulation of H1R gene expression.
Quercetin also inhibited
histamine- or PMA-induced phosphorylation of Tyr(311) of PKCδ and translocation of PKCδ to the Golgi. Pre-treatment with
quercetin for 3weeks suppressed TDI-induced nasal
allergy-like symptoms and elevation of H1R
mRNA in the nasal mucosa of TDI-sensitized rats. These data suggest that
quercetin suppresses H1R gene expression by the suppression of PKCδ activation through the inhibition of its translocation to the Golgi.