Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma.
Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma.
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类固醇抵抗性哮喘患者中性粒细胞中糖皮质激素的抗炎作用受损。
DOI：
10.1186/s12931-016-0462-0
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发表时间：
2016-11-16
影响因子：
5.8
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Wang M;Gao P;Wu X;Chen Y;Feng Y;Yang Q;Xu Y;Zhao J;Xie J
背景激素抵抗性哮喘（steroid resistant asthma，SR）是一种持续性气道炎症，经大剂量皮质激素治疗后仍不能缓解。此外，SR患者气道显示出增加的嗜中性粒细胞数量，其对糖皮质激素的反应较低。本研究旨在确定地塞米松（DEX）是否对中性粒细胞有不同的影响，从类固醇敏感性（SS）哮喘相比SR asthmatics.MethodsAdults哮喘（n= 38）被归类为SR或SS的基础上肺FEV 1%的变化，一个月的吸入皮质类固醇（ICS）治疗。在研究的首次访视期间从所有患者中采集血液样本。从血液中分离的中性粒细胞与地塞米松和/或特应性哮喘血清培养18小时。采用实时荧光定量PCR法检测促分裂原活化蛋白激酶磷酸酶-1（MKP-1）（糖皮质激素反式激活靶点）和糖皮质激素诱导的转录本1（GLCCI 1）（糖皮质激素诱导的细胞凋亡的早期标志物，其表达与哮喘患者吸入糖皮质激素的反应相关）的mRNA表达，并采用ELISA法检测上清液中促炎细胞因子IL-8的水平。流式细胞仪检测组成性中性粒细胞凋亡。ResultsDEX显着诱导MKP-1的表达在两个患者与SS和SR患者在一个浓度依赖性的方式，但更大的诱导观察SS患者在低浓度（10 - 6 M）。单纯哮喘血清无MKP-1表达，SR哮喘患者DEX诱导MKP-1表达受损。DEX或DEX/特应性哮喘血清组合均未诱导中性粒细胞表达GLCCI 1。与SR哮喘患者相比，DEX/特应性哮喘血清联合治疗的SS哮喘患者的中性粒细胞产生IL-8的抑制作用更大，尽管DEX单独治疗对SS和SR哮喘患者的中性粒细胞具有相同的作用。结论DEX对SS哮喘和SR哮喘患者中性粒细胞的作用不同，可能与糖皮质激素不敏感有关。
BackgroundSteroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics.MethodsAdults with asthma (n= 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment. Blood samples were collected from all patients during their first visit of the study. Neutrophils isolated from the blood were cultured with dexamethasone and/or atopic asthmatic serum for 18 h. The mRNA expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), a glucocorticoid transactivation target, and glucocorticoid-induced transcript 1 (GLCCI1), an early marker of glucocorticoid-induced apoptosis whose expression was associated with the response to inhaled glucocorticoids in asthma , was determined by real-time PCR, and ELISA was used to assess the pro-inflammatory cytokine IL-8 levels in the supernatant. Constitutive neutrophil apoptosis was detected by flow cytometry.ResultsDEX significantly induced MKP-1 expression in both patients with SS and SR patients in a concentration-dependent manner, but greater induction was observed for SS patients at a low concentration (10−6M). Asthmatic serum alone showed no MKP-1expression, and there was impaired induction of MKP-1 by DEX in SR asthma patients. The expression of GLCCI1 was not induced in neutrophils with DEX or DEX/atopic asthmatic serum combination. Greater inhibition of IL-8 production was observed in neutrophils from patients with SS asthma treated with DEX/atopic asthmatic serum combination compared with SR asthma patients, though DEX alone showed the same effect on neutrophils from SS and SR asthma patients. Meanwhile, DEX dependent inhibition of constitutive neutrophil apoptosis was similar between SS asthma and SR asthma patients.ConclusionsDEX exerted different effects on neutrophils from patients with SS asthma and SR asthma, which may contribute to glucocorticoid insensitivity.
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影响因子：
1.8
作者：
Lecoq, L.;Vincent, P.;Lavoie, J. -P.
通讯作者：
Lavoie, J. -P.
影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
影响因子：
7.3
作者：
Joshi, T.;Johnson, M.;Giembycz, M.
通讯作者：
Giembycz, M.
影响因子：
14.2
作者：
Chan, MTS;Leung, DYM;Spahn, JD
通讯作者：
Spahn, JD
DOI：
10.1164/ajrccm.160.5.9806170
发表时间：
1999-11-01
影响因子：
24.7
作者：
Jatakanon, A;Uasuf, C;Barnes, PJ
通讯作者：
Barnes, PJ