Prostaglandin D₂ pathway upregulation: relation to asthma severity, control, and TH2 inflammation.
Prostaglandin D₂ pathway upregulation: relation to asthma severity, control, and TH2 inflammation.
复制标题
DOI：
10.1016/j.jaci.2013.01.035
复制
发表时间：
2013-06
影响因子：
14.2
通讯作者：
Wenzel, Sally E.
中科院分区：
文献类型：
--
作者：
Fajt, Merritt L.;Gelhaus, Stacy L.;Freeman, Bruce;Uvalle, Crystal E.;Trudeau, John B.;Holguin, Fernando;Wenzel, Sally E.
关键词：
支气管肺泡灌洗（BAL）液前列腺素D2 （PGD2）水平在严重、控制不良的哮喘患者中升高，与上皮肥大细胞（MCs）有关。PGD2由造血前列腺素D合成酶（HPGDS）产生，作用于3g蛋白偶联受体，包括TH2淋巴细胞上表达的趋化受体同源分子（CRTH2）和PGD2受体1 （DP1）。然而，关于哮喘患者中这些通路元件的存在和激活，还有很多有待了解。我们试图比较支气管镜下从健康对照者和哮喘患者中获得的样本中PGD2途径元件的表达和激活，这些样本具有不同的疾病严重程度和控制，以及与TH2途径元件的关系。对上皮细胞和BAL液进行HPGDS（实时荧光定量PCR/免疫组织化学[IHC]）和PGD2 （ELISA/液相色谱质谱法）与MC蛋白酶水平的关系评估。检测两种炎症细胞受体DP1和CRTH2在管腔细胞中的表达。然后将这些PGD2途径标记物与哮喘严重程度、控制水平和TH2炎症标记物（血液嗜酸性粒细胞和呼出一氧化氮的比例）进行比较。证实先前的结果，BAL液中PGD2水平在严重哮喘患者中最高（总P = 0.0001）。上皮细胞间室HPGDS mRNA和IHC值各组间差异显著（P = 0.008和P < 0.0001），且与MC蛋白酶mRNA相关。重度哮喘患者CRTH2 mRNA和IHC值最高（P = 0.001和P = 0.0001）。哮喘加重、哮喘控制不良和TH2炎症标志物与较高的PGD2、HPGDS和CRTH2水平相关。目前的研究发现，在使用皮质类固醇的严重、控制不良、th2高哮喘患者中，PGD2通路的协同上调。
Bronchoalveolar lavage (BAL) fluid prostaglandin D2 (PGD2) levels are increased in patients with severe, poorly controlled asthma in association with epithelial mast cells (MCs). PGD2, which is generated by hematopoietic prostaglandin D synthase (HPGDS), acts on 3 G protein–coupled receptors, including chemoattractant receptor–homologous molecule expressed on TH2 lymphocytes (CRTH2) and PGD2 receptor 1 (DP1). However, much remains to be understood regarding the presence and activation of these pathway elements in asthmatic patients. We sought to compare the expression and activation of PGD2 pathway elements in bronchoscopically obtained samples from healthy control subjects and asthmatic patients across a range of disease severity and control, as well as in relation to TH2 pathway elements. Epithelial cells and BAL fluid were evaluated for HPGDS (quantitative real-time PCR/immunohistochemistry [IHC]) and PGD2 (ELISA/liquid chromatography mass spectrometry) in relation to levels of MC proteases. Expression of the 2 inflammatory cell receptors DP1 and CRTH2 was evaluated on luminal cells. These PGD2 pathway markers were then compared with asthma severity, level of control, and markers of TH2 inflammation (blood eosinophils and fraction of exhaled nitric oxide). Confirming previous results, BAL fluid PGD2 levels were highest in patients with severe asthma (overall P = .0001). Epithelial cell compartment HPGDS mRNA and IHC values differed among groups (P = .008 and P < .0001, respectively) and correlated with MC protease mRNA. CRTH2 mRNA and IHC values were highest in patients with severe asthma (P = .001 and P = .0001, respectively). Asthma exacerbations, poor asthma control, and TH2 inflammatory markers were associated with higher PGD2, HPGDS, and CRTH2 levels. The current study identifies coordinated upregulation of the PGD2 pathway in patients with severe, poorly controlled, TH2-high asthma despite corticosteroid use.
登录
查看更多内容
影响因子：
14.2
作者：
Abonia, J. Pablo;Blanchard, Carine;Butz, Bridget Buckmeier;Rainey, Heather F.;Collins, Margaret H.;Stringer, Keith;Putnam, Philip E.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
14.2
作者：
Dougherty, Ryan H.;Sidhu, Sukhvinder S.;Raman, Kavita;Solon, Margaret;Solberg, Owen D.;Caughey, George H.;Woodruff, Prescott G.;Fahy, John V.
通讯作者：
Fahy, John V.
DOI：
10.1016/j.jaci.2011.02.042
发表时间：
2011-08
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Moore WC;Evans MD;Bleecker ER;Busse WW;Calhoun WJ;Castro M;Chung KF;Erzurum SC;Curran-Everett D;Dweik RA;Gaston B;Hew M;Israel E;Mayse ML;Pascual RM;Peters SP;Silveira L;Wenzel SE;Jarjour NN;National Heart, Lung, and Blood Institute's Severe Asthma Research Group
通讯作者：
National Heart, Lung, and Blood Institute's Severe Asthma Research Group
DOI：
10.1124/jpet.111.187203
发表时间：
2012-02-01
影响因子：
3.5
作者：
Pettipher, Roy;Vinall, Shan L.;Hunter, Michael G.
通讯作者：
Hunter, Michael G.
影响因子：
4.8
作者：
Mahmud, I;Ueda, N;Hayaishi, O
通讯作者：
Hayaishi, O