論文

査読有り
2009年8月

Suplatast Tosilate Inhibits Histamine Signaling by Direct and Indirect Down-Regulation of Histamine H(1) Receptor Gene Expression through Suppression of Histidine Decarboxylase and IL-4 Gene Transcriptions

JOURNAL OF IMMUNOLOGY
  • Masum Shahriar
  • ,
  • Hiroyuki Mizuguchi
  • ,
  • Kazutaka Maeyama
  • ,
  • Yoshiaki Kitamura
  • ,
  • Naoki Orimoto
  • ,
  • Shuhei Horio
  • ,
  • Hayato Umehara
  • ,
  • Masashi Hattori
  • ,
  • Noriaki Takeda
  • ,
  • Hiroyuki Fukui

183
3
開始ページ
2133
終了ページ
2141
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.4049/jimmunol.0901058
出版者・発行元
AMER ASSOC IMMUNOLOGISTS

Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as sneezing, congestion, and rhinorrhea. Histamine plays important roles in eliciting AR symptoms. Up-regulation of the histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines are also involved in the pathogenesis of AR. We examined the effect of suplatast tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene-2,4-diisocyan ate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R. Provocation with TDI increased nasal symptoms, HDC activity, the histamine content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs. Suplatast also suppressed HDC activity in the nasal mucosa and the histamine content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal cavity of normal rats up-regulated H1R mRNA, while intranasal application of histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA elevation. These results suggest that suplatast alleviates nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through the suppression of histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL-4 gene transcriptions, respectively. The Journal of Immunology, 2009, 183: 2133-2141.


リンク情報
DOI
https://doi.org/10.4049/jimmunol.0901058
CiNii Articles
http://ci.nii.ac.jp/naid/120004710271
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19596986
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000268519500073&DestApp=WOS_CPL
ID情報
  • DOI : 10.4049/jimmunol.0901058
  • ISSN : 0022-1767
  • CiNii Articles ID : 120004710271
  • PubMed ID : 19596986
  • Web of Science ID : WOS:000268519500073

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