2022 Fiscal Year Final Research Report

Effect of IL-33 Gene Expression suppression on allergic rhinitis

Research Project

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Project/Area Number	20K09693
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56050:Otorhinolaryngology-related
Research Institution	The University of Tokushima
Principal Investigator	KITAMURA Yoshiaki 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (60380028)
Co-Investigator(Kenkyū-buntansha)	武田憲昭徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30206982) 水口博之大阪大谷大学, 薬学部, 教授 (40247838) 福井裕行大阪大谷大学, 薬学部, 研究員 (90112052) 神村盛一郎徳島大学, 病院, 助教 (90867194)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	アレルギー性鼻炎
Outline of Final Research Achievements	Allergic rhinitis affects approximately 50% of the Japanese population. The important role of eosinophils for late phase reaction of allergic rhinitis has been reported. Leukotrienes released from eosinophils cause nasal mucosal swelling, observed in a late phase. Previously, we demonstrated that the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis. We found d PMA induced IL-33 gene upregulation and the effect of inhibitor of protein kinase C and heat shock protein 90 on the PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. We then used house dust mite antigen‐induced mouse models of allergic rhinitis. Intranasal sensitization and chronic mite antigen challenge caused nasal symptoms and eosinophilic inflammation. These findings suggest that they could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression.
Free Research Field	アレルギー
Academic Significance and Societal Importance of the Research Achievements	アレルギー性鼻炎は国民の約1/2が罹患する国民病であり、鼻症状で最も難治の鼻閉は好酸球性炎症の関与が大きい。治療抵抗性の鼻閉を改善するためには、アレルギー性鼻炎における鼻粘膜の好酸球性炎症の病態の解明とその治療法の開発が必要である。我々はアレルギー性鼻炎患者の鼻粘膜のIL-33遺伝子発現の亢進が末梢血好酸球数の増加と相関することを明らかにし、蛋白キナーゼCδシグナル抑制薬によりIL-33遺伝子発現亢進を抑制できることを明らかにしたことから、蛋白キナーゼCδシグナル抑制薬は鼻粘膜のIL-33遺伝子発現の亢進を抑制し、好酸球性炎症を抑制することでアレルギー性鼻症状を抑制する効果が期待される。