論文

査読有り
2010年4月

Interleukin-4 up-regulates histamine H1 receptors by activation of H1 receptor gene transcription

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
  • Shuhei Horio
  • ,
  • Katsumi Fujimoto
  • ,
  • Hiroyuki Mizuguchi
  • ,
  • Hiroyuki Fukui

381
4
開始ページ
305
終了ページ
313
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00210-010-0491-z
出版者・発行元
SPRINGER

Histamine plays an important role in allergy mainly through histamine H1 receptor (H1R). Recent studies showed that the H1R level is elevated in allergic conditions, suggesting that this will make the allergic symptoms worse by intensifying H1R-mediated processes. Some cytokines are also involved in allergy, and interleukin-4 (IL-4) has been implicated as an important mediator of allergic inflammation. It is noteworthy that the level of IL-4 is elevated under allergic states. We tested whether IL-4 has a role in up-regulating H1R level by using the cultured human HeLa cell as a model system that expresses both IL-4 receptor and H1R. IL-4 stimulation increased H1R protein levels and H1R mRNA levels. IL-4 also increased H1R promoter activity, but had no effect on H1R mRNA stability, indicating that up-regulation of H1R was due to an increase in H1R mRNA synthesis. IL-4 activated STAT6 (signal transducer and activator of transcription 6) in HeLa cells, and up-regulation of H1R mRNA and activation of STAT6 by IL-4 were inhibited by a specific JAK3 (Janus-activated kinase 3) inhibitor. Stimulation with histamine also up-regulated H1R mRNA, and co-stimulation with histamine and IL-4 elevated H1R mRNA level significantly higher than the stimulation with histamine or IL-4 alone did. These results indicated that IL-4 up-regulated H1R mRNA level through increased transcription of H1R gene via JAK3-STAT6 pathway. The effects of histamine and IL-4 were additive, suggesting that these allergic mediators will work together to up-regulate H1R level, and thus make the allergic symptom worse by intensifying H1R-mediated allergic processes.


リンク情報
DOI
https://doi.org/10.1007/s00210-010-0491-z
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000277181700003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1007/s00210-010-0491-z
  • ISSN : 0028-1298
  • Web of Science ID : WOS:000277181700003

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