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

Naunyn-Schmiedeberg's Archives of Pharmacology
Shuhei HorioHiroyuki Fukui

Abstract

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 t...Continue Reading

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Citations

Nov 8, 2012·Mediators of Inflammation·Hideaki ShirasakiTetsuo Himi
Mar 5, 2016·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·J H KookS H Lee
Feb 16, 2015·Cellular and Molecular Neurobiology·Marcelo Gomes GranjaElizabeth Giestal-de-Araujo
Aug 10, 2011·The Journal of Allergy and Clinical Immunology·Liam O'MahonyCezmi A Akdis
May 27, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ju Wan KangHyung-Ju Cho

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