Allergic rhinitis （AR） is a type I allergic disease of the nasal mucosa, characterized by sneezing, watery rhinorrhea, and nasal congestion. A recent epidemiological survey revealed that nearly half of the population develops AR in Japan. Histamine is a major chemical mediator that induces AR symptoms by binding to histamine H1 receptor （H1R） during the development of AR. We found that histamine-mediated stimulation of H1R induces upregulation of H1R gene expression through the activation of protein kinase Cδ, and that the elevated receptor expression levels in the nasal mucosa enhance histamine signaling, thereby exacerbating AR symptoms. Antihistamines not only block histamine signaling through H1R but also suppress histamine-induced upregulation of H1R transcriptional activation. Moreover, they exert a suppressive effect on basal H1R transcription in the absence of histamine, which may be part of their inverse agonist action. Recently, light-emitting diodes that emit energy at a wavelength of 310 nm, corresponding to narrowband-ultraviolet B （NB-UVB）, have been developed, and these devices are small enough to be used for intranasal phototherapy. To develop a phototherapy using NB-UVB for the treatment of AR, we examined the effects of NB-UVB irradiation on H1R gene expression. Our findings demonstrated that low-dose NB-UVB irradiation suppressed PMA-induced upregulation of H1R mRNA in a wavelength-specific, dose-dependent, and reversible manner, without inducing apoptosis. We then conducted an in vivo study using a rat AR model. Our findings demonstrated that intranasal pre-irradiation with NB-UVB dose-dependently suppressed upregulation of H1R mRNA in the nasal mucosa, leading to the alleviation of nasal symptoms without causing DNA damage. These findings suggest that phototherapy with low-dose NB-UVB can be applied effectively and safely for the treatment of AR. Since phase I and early phase II clinical trials confirmed its safety, we are currently conducting an investigator-initiated clinical trial in patients with pollinosis.
"},{"@language":"ja","@value":"アレルギー性鼻炎は，くしゃみ，水様性鼻漏，鼻閉を3主徴としたⅠ型アレルギー疾患であり，通年性アレルギー性鼻炎と季節性アレルギー性鼻炎に分けられる。アレルギー性鼻炎の有病率は，1998年に29．8％であったが，2008年に39．4％，2019年には49．2％と増加し，今や国民の約2人に1人が罹患している国民病となっている1）。1964年に初めて報告されたスギ花粉症の有病率は1998年には16．2％であったが，2008年に26．5％，2019年には38．8％と顕著に増加している。10代は約半数が発症しており，5-9歳の有病率も30．1％まで急増し，発症は低年齢化している。またスギ花粉以外の花粉症も1998年は10．9％であったが，2008年に15．4％，2019年には25．1％と増加している。そこで日本耳鼻咽喉科頭頸部外科学会では花粉症重症化ゼロ作戦と称して2030年までに重症化ゼロを目指したキャンペーンを開始した。また，政府も花粉症に関する関係閣僚会議を開いて発生源対策，飛散対策，発症・曝露対策の花粉症対策3本柱を打ち出した。一方，主にダニ抗原による通年性アレルギー性鼻炎の有病率は1998年に18．7％，2008年には23．4％と増加したが，2019年は24．5％と横ばいになっている。 本稿ではアレルギー性鼻炎の病態の解明，特にアレルギー性鼻炎の発症におけるヒスタミンによる鼻粘膜ヒスタミンH1受容体（H1受容体）発現亢進の分子機構と花粉症の初期療法のメカニズムについて，またわれわれが開発している新規治療法であるナローバンドUVBを発光するLEDを用いた光治療装置について概説する。
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