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Chronic airway inflammation regulated by proton-sensing receptors

质子敏感受体调节的慢性气道炎症

基本信息

批准号：
18591099
负责人：
ISHIZUKA Tamotsu
金额：
$ 2.57万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591099/
关键词：
Bronchial asthma Proton-sensing receptor OGR1 Bronchial smooth muscle Resolvin E1 IL-6 IL-13 OGR1 Resolvin El プロトン受容体気道炎症気管支平滑筋細胞気道上皮細胞ケモカイン

项目摘要

Acidification of airway systems has been reported to be associated with bronchial asthma and low pH could be contributed substantially to airway inflammation. To evaluate the mRNA expression of proton sensing G-protein-coupled receptors in human smooth muscle cells (SSMC) and bronchial epithelial cells, real-time PCR was performed. OGR1 was predominantly expressed in BSMC. Extracellular acidic pH induced IL -6 production and it was markedly inhibited by sIRNA specific OGR1. To investigate the role of OGR1 in chronic airway inflammation, especially bronchial asthma, a murine allergic asthma model sensitized with ovalbumin (OVA) was studied. We are comparing OGR1 knock-out BALB/c mice and wild mice in airway responsiveness to inhaled methacholine, inflammatory cells accumulation in bronchoalveolar lavage fluid (BALF), histology, anti-OVA IgE, and cytokines in BALF. On the other hand, we were interested in the effect of rsolvin E1, an anti-inflammatory lipid mediator, on airway inflammation. In a murine allergic asthma model, resolvin E1 inhibited eosinophil and lymphocyte recruitment, IL-13 in BALF, OVA specific IgE in serum as well as airway hyperfesposiveness to inhaled methacholine. Moreover, resolvin E1-treated mice had significantly lower mucus scores compared to vehicle-treated mice based on the number of goblet cells stained with PAS.

据报道，气道系统的酸化与支气管哮喘有关，低pH值可能是气道炎症的主要原因。为了评估质子敏感G蛋白偶联受体在人平滑肌细胞（SSMC）和支气管上皮细胞中的mRNA表达，进行实时PCR。OGR 1主要表达于BSMC。细胞外酸性pH可诱导IL-6的产生，并被sIRNA特异性OGR 1显著抑制。为探讨OGR 1在慢性气道炎症尤其是支气管哮喘中的作用，本研究采用卵白蛋白（OVA）致敏的小鼠过敏性哮喘模型。我们比较了OGR 1基因敲除BALB/c小鼠和野生小鼠对吸入乙酰甲胆碱的气道反应性、支气管肺泡灌洗液（BALF）中炎性细胞积聚、组织学、抗OVA IgE和BALF中细胞因子。另一方面，我们感兴趣的是rsolvin E1，一种抗炎脂质介质，对气道炎症的影响。在小鼠过敏性哮喘模型中，resolvin E1抑制嗜酸性粒细胞和淋巴细胞的募集，BALF中的IL-13，血清中的OVA特异性IgE以及吸入乙酰甲胆碱的气道高阳性。此外，基于PAS染色的杯状细胞数量，消退素E1处理的小鼠的粘液评分显著低于溶剂处理的小鼠。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lysophosphatidic acid inhibits RANTES production in human bronchialepithelial cells through a Rho-dependent pathway

溶血磷脂酸通过 Rho 依赖性途径抑制人支气管上皮细胞中 RANTES 的产生

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Tamotsu Ishizuka;et. al.
通讯作者：
et. al.

Lysophosphatidic acid inhibits RANTES production in human bronchial epithelial cells through a Rho-dependent pathway

溶血磷脂酸通过 Rho 依赖性途径抑制人支气管上皮细胞中 RANTES 的产生

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Tamotsu Ishizuka;Fumikazu Okajima;Tadayoshi Kawata;Takeshi Hisada;Noriko Yanagitani;Kyoichi Kaira;Mitsuyoshi Utsugi;Noriaki Sunaga;Kunio Dobashi;Masatomo Mori.
通讯作者：
Masatomo Mori.

Resolvin El dampens airway inflammation and hyperresponsiveness in a mu rine model of asthma.

Resolvin El 可抑制小鼠哮喘模型中的气道炎症和高反应性。

DOI：
发表时间：
2008
期刊：
Biochem Biophys Res Commun. 367
影响因子：
0
作者：
Aoki H;Hisada T;IshiZuka T;Utsugi M;Kawata T;Shimizu Y;Okajima F;Dobashi K;Mori M.
通讯作者：
Mori M.

Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma