Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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.
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