The role of novel redox molecules in the airway of patients with ACO

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17208
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Kyogoku Yorihiko 東北大学, 大学病院, 特任助手 (20849400)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 活性イオウ分子種（RSS） / 活性窒素種（RNS) / ACO / ステロイド抵抗性

Outline of Final Research Achievements

Compared with lung tissue and sputum derived from healthy subjects, patients with ACO showed a decrease in percentages of RSS-producing enzyme-positive cells, an increase in NFκB expression, a decrease in GR expression, and a decrease in HDAC2 activity. Furthermore, in BEAS-2B cells with decreased RSS-producing enzyme expression, enhanced NFκB expression, decreased GR expression, and decreased HDAC2 activity were observed. Currently, we are investigating changes in RNS production model, NFκB / GR expression after steroid pretreatment, HDAC2 activity, and anti-inflammatory effect. Furthermore, RSS-producing enzymes are overexpressed, and the effects of NFκB / GR expression, HDAC2 activity, and the degree of anti-inflammatory effect after steroid pretreatment are under investigation. It is suggested that decreased RSS production may be involved in steroid resistance through enhanced NFκB expression, decreased GR expression, and decreased HDAC2 activity.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

ACOは頻回の増悪・入院により医療コストがかかることが問題の一つであり、ステロイド抵抗性を改善させるような新規治療が望まれる。RSSの産生低下はNFκB発現増強、GR発現減弱、HDAC2の活性低下を介したステロイド抵抗性の基盤を成しており、RSSの外的投与によりこれを改善させる可能性がある。本検討はACOをはじめとするステロイド抵抗性を示す病態に対する新規治療薬の開発への基礎となると考えられる。