Expression of corticosteroid-regulated genes by PBMCs in children with asthma.
Expression of corticosteroid-regulated genes by PBMCs in children with asthma.
复制标题
DOI：
10.1016/j.jaci.2018.06.043
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Busse WW
中科院分区：
文献类型：
--
作者：
Goleva E;Babineau DC;Gill MA;Jackson LP;Shao B;Hu Z;Liu AH;Visness CM;Sorkness CA;Leung DYM;Togias A;Busse WW
吸入性皮质类固醇(ICSS)反应的变异性可能导致哮喘控制不佳。开发评估皮质类固醇治疗效果的生物标志物是很重要的。我们试图研究PBMC对糖皮质激素的体外反应是否与临床ICS反应有关。收集125名6-17岁哮喘儿童在登记时(访问0[V0])和为期一年的双月指南管理访问(访问6[V6])的PBMC。难以控制和易于控制的哮喘被定义为每天需要500μg或更多的丙酸氟替卡松(Flu)加或不加长效β激动剂治疗，而在至少4次就诊中需要100μg或更少的Flu。采用逆转录聚合酶链式反应技术检测糖皮质激素受体α、皮质类固醇激素反式激活(FK506结合蛋白5)和转录抑制标志物(IL-8和肿瘤坏死因子-α)在新鲜分离细胞和10−8mol/L Flu作用下的表达水平。与易控哮喘组相比，难治性哮喘组PBMC糖皮质激素受体α水平V0显著降低(P=0.05)。在易于控制的哮喘患者中，观察到Flu对IL-8的抑制增加了30%(P=0.04)，V0和V6之间的Flu对肿瘤坏死因子-α的抑制有增加的趋势(P=0.07)。在难治性哮喘患者中，IL-8的V0和V6无明显变化，流感对肿瘤坏死因子-α的抑制作用也无明显变化。激素介导的反式激活(流感诱导的FK506结合蛋白5)在难以控制和易控制的哮喘患者的V0和V6之间增加(分别为P=0.05和P=0.03)。对于难以控制的哮喘儿童，采用基于指南的治疗并需要大剂量ICSS治疗的PBMC在体外对皮质类固醇的反应性降低。
Variability in response to inhaled corticosteroids (ICSs) can result in less than optimal asthma control. Development of biomarkers assessing the therapeutic efficacy of corticosteroids is important. We sought to examine whether in vitro PBMC responses to corticosteroids relate to the clinical ICS response. PBMCs were collected from 125 children with asthma (6–17 years) at enrollment (visit 0 [V0]) and after 1 year of bimonthly guidelines-based management visits (visit 6 [V6]). Difficult-to-control and easy-to-control asthma were defined as requiring daily therapy with 500 μg or more of fluticasone propionate (FLU) with or without a long-acting β-agonist versus 100 μg or less of FLU in at least 4 visits. mRNA levels of glucocorticoid receptor α and corticosteroid transactivation (FK506-binding protein 5) and transrepression markers (IL-8 and TNF-α) were measured by using RT-PCR in freshly isolated cells and in response to 10−8 mol/L FLU. Compared with PBMCs from patients with easy-to-control asthma, PBMCs from those with difficult-to-control asthma had significantly lower glucocorticoid receptor α levels at V0 (P = .05). A 30% increase in IL-8 suppression by FLU (P = .04) and a trend for increased TNF-α suppression by FLU between V0 and V6 (P = .07) were observed in patients with easy-to-control asthma. In contrast, no changes between V0 and V6 in IL-8 and TNF-α suppression by FLU were observed in patients with difficult-to-control asthma. Corticosteroid-mediated transactivation (FK506-binding protein 5 induction by FLU) increased in the PBMCs of patients with difficult-to-control and easy-to-control asthma between V0 and V6 (P = .05 and P = .03, respectively). PBMCs of children with difficult-to-control asthma treated with guidelines-based therapy and requiring high-dose ICSs had reduced in vitro responsiveness to corticosteroids.
登录
查看更多内容
DOI：
10.1016/j.jaci.2008.07.007
发表时间：
2008-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Goleva E;Hauk PJ;Hall CF;Liu AH;Riches DW;Martin RJ;Leung DY
通讯作者：
Leung DY
组蛋白脱乙酰基酶2介导的糖皮质激素受体的脱乙酰基化可以抑制NF-kappab。
影响因子：
15.3
作者：
Ito, Kazuhiro;Yamamura, Satoshi;Essilfie-Quaye, Sarah;Cosio, Borja;Ito, Misako;Barnes, Peter J;Adcock, Ian M
通讯作者：
Adcock, Ian M
影响因子：
14.2
作者：
Chang, Timothy S.;Lemanske, Robert F., Jr.;Mauger, David T.;Fitzpatrick, Anne M.;Sorkness, Christine A.;Szefler, Stanley J.;Gangnon, Ronald E.;Page, C. David;Jackson, Daniel J.
通讯作者：
Jackson, Daniel J.
DOI：
10.1164/rccm.200507-1046oc
发表时间：
2006-03-15
影响因子：
24.7
作者：
Goleva, E;Li, LB;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
14.2
作者：
Berry, Alalia;Busse, William W.
通讯作者：
Busse, William W.