Molecular Mechanisms of Transcriptional Upregulation of the Histamine H<sub>1</sub> Receptor Gene in the Development of Allergic Rhinitis

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  • アレルギー性鼻炎におけるヒスタミンH<sub>1</sub>受容体遺伝子発現亢進の分子機構とその制御
  • アレルギー性鼻炎におけるヒスタミンH₁受容体遺伝子発現亢進の分子機構とその制御
  • アレルギーセイ ビエン ニ オケル ヒスタミン H ₁ ジュヨウタイ イデンシ ハツゲン コウシン ノ ブンシ キコウ ト ソノ セイギョ

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<p>Histamine is a major chemical mediator involved in the development of allergic rhinitis, inducing the symptoms of allergic rhinitis through binding to the histamine H1 receptor (H1R). H1R is a rate-limiting molecule in histamine signaling, with the signaling increased with elevated receptor expression levels. We found that histamine-mediated stimulation of H1R induced upregulation of the H1R gene through protein kinase Cδ (PKCδ) activation, and that the elevated receptor expression levels in the nasal mucosa increased histamine signaling to further exacerbate the symptoms of allergic rhinitis. Antihistamines have three effects: they block histamine signaling mediated by H1R; they suppress histamine-induced upregulation of transcriptional activation of H1R; they suppress basal transcription of H1R even in the absence of histamine. The third effect may be a part of the inverse agonist action of antihistamines. Dexamethasone inhibits both basal transcription and transcriptional activation of H1R through suppression of extracellular signal-regulated kinase phosphorylation. We also found that pre-seasonal prophylactic treatment with antihistamines or intranasal corticosteroid sprays suppressed the gene expression of H1R in the nasal mucosa, resulting in the suppression of nasal symptoms in patients with cedar pollen pollinosis. Because H1R is an allergic rhinitis disease-sensitive gene, a new treatment strategy for allergic rhinitis targeting PKCδ has been suggested.</p>

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