The involvement of proton-sensing receptor OGR1 in chronic airway inflammation and secretion.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09213
• 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 Fukui
• Principal Investigator: ISHIZUKA TAMOTSU 福井大学, 学術研究院医学系部門, 教授 (50302477)
• Co-Investigator(Renkei-kenkyūsha): OKAJIMA Fumikazu 青森大学, 薬学部, 教授 (30142748)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: プロトン / OGR1 / 気道炎症 / IL-8 / 気管支平滑筋細胞 / グルココルチコイド

Outline of Final Research Achievements

Human bronchial smooth muscle cells (BSMCs) are involved in airway inflammatio mation. Ovarian cancer G protein-coupled receptor 1 (OGR1) sense extracellular protons and mediate cytokine production in BSMCs. BSMCs were stimulated by pH 6.3 or pH 7.4-adjusted DMEM containing 0.1% BSA (0.1% BSA-DMEM). As a control stimulant, TNF-alpha (10 ng/ml) was used. IL-8 mRNA expression in BSMCs was quantified by RT-PCR. Acidic pH induced mRNA expression of IL-8 and a substantial amount of IL-8 production in BSMCs. BSMCs transfected by siRNA specific for OGR1 produced less IL-8 compared with those transfected non-targeting siRNA. PKC inhibitor, MEK 1/2 inhibitor, and the inhibitor of IkB phosphorylation reduced acidic pH-stimulated IL-8 production in BSMCs. Dexamethasone inhibited acidic pH-stimulated IL-8 production of BSMCs in a dose-dependent manner. Dexamethasone did not affect either phosphorylation or binding to consensus DNA site of NF-kB p65.

Free Research Field

呼吸器内科学