Orimoto, Naoki Tokushima University|Taiho Pharmaceutical Co. LTD.
Kadota, Takuya Tokushima University
Kominami, Takahiro Tokushima University
Das, Asish K. Tokushima University|Khulna University
Sawada, Akiho Tokushima University
Tamada, Misaki Tokushima University
Miyagi, Kohei Tokushima University
Adachi, Tsubasa Tokushima University
Matsumoto, Mayumi Tokushima University
Kosaka, Tomoya Tokushima University
Kitamura, Yoshiaki Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Takeda, Noriaki Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine.
Journal of Pharmacological Sciences
Japanese Pharmacological Society|Elsevier
© 2016 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
|DOI (Published Version)|
|URL ( Publisher's Version )|
jphs_130_3_151.pdf 1000 KB