Role of IL-17F in severe asthma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Kawaguchi Mio 筑波大学, 医学医療系, 講師 (50365748)
• Research Collaborator: NAKAJIMA Masayuki ; FUJITA Junichi ; OTA Kyoko ; HIZAWA Nobuyuki
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 難治性喘息 / インターロイキン17Ｆ / 気道平滑筋 / インターロイキン8 / P-TEFb / ステロイド

Outline of Final Research Achievements

IL-17F is involved in the pathogenesis ofsevere asthma. However, the effects of steroids on the function of IL-17F signaling mechanisms are largely unknown. One of the transcription elongation factors, P-TEFb composed of cyclin T1 and CDK9, is known as a novel checkpoint regulator of gene expression via Brd4. We reported that IL-17F markedly induced the expression of the IL-8 in human airway smooth muscle cells . Pretreatment of CDK9 inhibitor and transfection of siRNAs targeting CDK9 abrogated IL-17F-induced IL-8 production. Transfection of siRNAs targeting Brd4 and cyclin T1 diminished IL-17F-induced phosphorylation of CDK9 and IL-8 production. Moreover, budesonide decreased CDK9 phosphorylation and markedly inhibited IL-17F-induced IL-8 production. P-TEFb is involved in IL-17F-induced IL-8 expression and that steroids diminish it via the inhibition of CDK9 phosphorylation. IL-17F and P-TEFb might be novel therapeutic targets for severe asthma.

Free Research Field

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