Therapeutic application to cystic fibrosis based on IL-37 and stabilized cell surface expression of SIGIRR

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Sojo University
• Principal Investigator: SHUTO Keiko 崇城大学, 薬学部, 講師 (70510692)
• Research Collaborator: KAI Hirofumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 嚢胞性線維症（CF） / SIGIRR / IL-37b

Outline of Final Research Achievements

Cystic Fibrosis (CF) is an inherited disorder characterized by chronic airway inflammation, which is partly due to the defective expression or function of negative regulators of toll-like receptor (TLR) that induce inflammatory signaling. In this study, we focused on SIGIRR and anti-inflammatory cytokine IL-37b, which work as a negative regulator of TLR signaling and it's ligand respectively, and functionally analyzed anti-inflammatory IL-37b-SIGIRR pathway in CF. As a result, anti-inflammatory activity via IL-37b-SIGIRR pathway was abrogated in CF airway epithelial cells due to the augmented expression of mutant SIGIRR, which causes the decrease in it's cell surface expression in CF.

Free Research Field

細胞生物学、分子生物学、薬理学

Academic Significance and Societal Importance of the Research Achievements

近年CFの原因遺伝子に対する治療薬が認可され根治治療への期待が高まる一方、未だ解決できない問題として挙げられているのが、CF患者の多くで認められる感染症およびそれに伴う慢性炎症である。故にCF炎症の分子基盤の解明および感染・炎症を調節する因子の探索は、今後ますます重要となることが予想される。本研究は、未だCF研究領域において報告のないSIGIRRおよびIL37bを標的とした新たな炎症治療薬法を模索する初めての試みである。