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ID 115427
Title Alternative
Pyrogallol inhibits NFAT signal
Author
Nakano, Tomohiro Tokushima University
Ikeda, Mitsuhiro Tokushima University
Wakugawa, Tomoharu Tokushima University
Kaminuma, Osamu Hiroshima University
Kitamura, Noriko The Tokyo Metropolitan Institute of Medical Science
Keywords
allergic rhinitis
calcineurin
histamine H1 receptor gene
Interleukin-9 gene
nuclear factor of activated T-cells
Content Type
Journal Article
Description
As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
Publisher
Tokushima University Faculty of Medicine
Volume
67
Issue
3-4
Start Page
289
End Page
297
Sort Key
289
Published Date
2020-08
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Pharmaceutical Sciences
Medical Sciences