Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis.
As expression level of allergic disease-sensitive genes are correlated with allergic symptom severity, suppression of these gene expressions could be good therapeutics. We have demonstrated that PKCδ signaling and NFAT signaling, involve in histamine H1 receptor (H1R) and IL-9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti-allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ-mediated H1R and NFAT-mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up-regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa-tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti-allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression. J. Med. Invest. 65:242-250, August, 2018.
['Islam|Rezwanul|R|', 'Mizuguchi|Hiroyuki|H|', 'Shaha|Aurpita|A|', 'Nishida|Kohei|K|', 'Yabumoto|Masami|M|', 'Ikeda|Hisashi|H|', 'Fujino|Hiromichi|H|', 'Kitamura|Yoshiaki|Y|', 'Fukui|Hiroyuki|H|', 'Takeda|Noriaki|N|']
D032421:Ampelopsis D000818:Animals D002460:Cell Line D016207:Cytokines D005786:Gene Expression Regulation D006367:HeLa Cells D006801:Humans D000067596:Interleukin-33 D008297:Male D051379:Mice D008517:Phytotherapy D010936:Plant Extracts D012333:RNA, Messenger D051381:Rats D011914:Rats, Inbred BN D011969:Receptors, Histamine H1 D065631:Rhinitis, Allergic D015398:Signal Transduction D041701:Swiss 3T3 Cells D000069460:Teas, Medicinal
histamine H1 receptor Allergic rhinitis Interleukin‐33 nuclear factor of activated T‐cells protein kinase Cδ