p-STAT6、PU.1和核因子κB参与哮喘患者变应原诱导的迟发性气道炎症。
p-STAT6, PU.1, and NF-κB are involved in allergen-induced late-phase airway inflammation in asthma patients.
作者信息
Hoppenot Deimante, Malakauskas Kestutis, Lavinskiene Simona, Sakalauskas Raimundas
机构信息
Department of Pulmonology and Immunology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Laboratory of Pulmonology, Department of Pulmonology and Immunology, Medical Academ, Lithuanian University of Health Sciences, Kaunas, Lithuania.
出版信息
BMC Pulm Med. 2015 Oct 14;15:122. doi: 10.1186/s12890-015-0119-7.
BACKGROUND
Previous in vitro and animal studies demonstrated that transcription factors p-STAT6 and PU.1 are required to induce interleukin (IL)-9 secretion by T helper (Th) 9 cells. It is believed that n factor-kappaB (NF-κB) plays a role in eosinophil survival. The importance of these transcription factors in the pathogenesis of allergic asthma (AA) in humans is poorly understood. We evaluated p-STAT6 and PU.1 expression in peripheral blood Th9 cells and NF-κB expression in eosinophils during late-phase airway inflammation in AA patients.
METHODS
Nineteen adults with AA and 14 adult healthy individuals (HI) were examined. Peripheral blood collected 24 h before (baseline) and 24 h after bronchial allergen challenge. CD4(+) cells and eosinophils were isolated by high-density gradient centrifugation and magnetic separation. The percentage of Th9 cells and apoptotic eosinophils was estimated by flow cytometry. p-STAT6 and PU.1 expression was expressed as mean fluorescence intensity (MFI) in Th9 cells. NF-κB levels were expressed as MFI in peripheral blood eosinophils. Serum IL-9 and IL-5 levels were determined by enzyme-linked immunosorbent assay.
RESULTS
At baseline, MFI of p-STAT6 and PU.1 in peripheral blood Th9 cells and MFI of NF-κB in eosinophils and, serum IL-5 and IL-9 levels were greater in AA patients (P < 0.05). Decreased eosinophil apoptosis was seen in the AA group compared with HI (P < 0.05). MFI of p-STAT6, PU.1, and NF-κB and serum levels of IL-5 and IL-9 were increased in the AA group 24 h after challenge compared with baseline (P < 0.05). In the AA group, a correlation between serum IL-9 and Th9 cells (r = 0.7, P = 0.001) and MFI of PU.1 (r = 0.6, P = 0.01) 24 h after bronchial allergen challenge was observed. A correlation between Th9 cells and MFI of p-STAT6 (r = 0.45, P = 0.03) as well as MFI of PU.1 (r = 0.5, P = 0.02) 24 h after challenge was only observed in AA patients. A correlation between the MFI of NF-κB and eosinophil apoptosis was observed in AA patients 24 h before (r = - .46, P = 0.02) and after (r = -0.5, P = 0.02) challenge.
DISCUSSIONS
p-STAT6 and PU.1 may be associated with Th9 cells and IL-9 production, whereas NF-κB and IL-5 may be associated with reduced eosinophil apoptosis in allergen-induced late-phase airway inflammation.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02214303.
背景
先前的体外和动物研究表明，转录因子p-STAT6和PU.1是诱导辅助性T（Th）9细胞分泌白细胞介素（IL）-9所必需的。据信，核因子-κB（NF-κB）在嗜酸性粒细胞存活中起作用。这些转录因子在人类过敏性哮喘（AA）发病机制中的重要性尚不清楚。我们评估了AA患者晚期气道炎症期间外周血Th9细胞中p-STAT6和PU.1的表达以及嗜酸性粒细胞中NF-κB的表达。
方法
对19名成年AA患者和14名成年健康个体（HI）进行检查。在支气管过敏原激发前24小时（基线）和激发后24小时采集外周血。通过高密度梯度离心和磁性分离分离CD4(+)细胞和嗜酸性粒细胞。通过流式细胞术估计Th9细胞和凋亡嗜酸性粒细胞的百分比。p-STAT6和PU.1的表达以Th9细胞中的平均荧光强度（MFI）表示。NF-κB水平以外周血嗜酸性粒细胞中的MFI表示。通过酶联免疫吸附测定法测定血清IL-9和IL-5水平。
结果
在基线时，AA患者外周血Th9细胞中p-STAT6和PU.1的MFI以及嗜酸性粒细胞中NF-κB的MFI以及血清IL-5和IL-9水平更高（P < 0.05）。与HI相比，AA组中嗜酸性粒细胞凋亡减少（P < 0.05）。与基线相比，激发后24小时AA组中p-STAT6、PU.1和NF-κB的MFI以及血清IL-5和IL-9水平升高（P < 0.05）。在AA组中，观察到支气管过敏原激发后24小时血清IL-9与Th9细胞之间的相关性（r = 0.7，P = 0.001）以及PU.1的MFI（r = 0.6，P = 0.01）。仅在AA患者中观察到激发后24小时Th9细胞与p-STAT6的MFI（r = 0.45，P = 0.03）以及PU.1的MFI（r = 0.5，P = 0.02）之间的相关性。在AA患者中，激发前24小时（r = -0.46，P = 0.02）和激发后（r = -0.5，P = 0.02）观察到NF-κB的MFI与嗜酸性粒细胞凋亡之间的相关性。
讨论
p-STAT6和PU.1可能与Th9细胞和IL-9产生相关，而NF-κB和IL-5可能与过敏原诱导的晚期气道炎症中嗜酸性粒细胞凋亡减少相关。
试验注册
ClinicalTrials.gov NCT02214303。
Zotero 插件