Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.
Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.
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DOI：
10.1371/journal.pone.0104080
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Carella M
中科院分区：
文献类型：
--
作者：
Conese M;Castellani S;Lepore S;Palumbo O;Manca A;Santostasi T;Polizzi AM;Copetti M;Di Gioia S;Casavola V;Guerra L;Diana A;Montemurro P;Mariggiò MA;Gallo C;Maffione AB;Carella M
为了寻找对抗生素治疗敏感的囊性纤维化（CF）肺部炎症性疾病的更特异性生物标志物，我们试图评估CF患者治疗前与非CF健康个体和抗生素治疗后中性粒细胞的基因表达谱。参与中性粒细胞介导的炎症的基因，即趋化性、呼吸爆发、细胞凋亡和颗粒胞吐，是本研究的目标。对CF患者和对照组的血液和气道中性粒细胞进行微阵列分析。使用1.4倍变化（log）阈值和p<0.05的截止值来识别显著基因。使用社区网络和主成分分析来区分对照组、治疗前和治疗后患者组。对照组和治疗前的CF患者很容易分开，而抗生素治疗前后的患者之间不可能有明确的区分。与对照组相比，治疗前血液中性粒细胞中有269个基因下调，56个基因上调。同一患者治疗前后的比较显示，44个基因下调，72个基因上调。三个基因似乎对治疗敏感并恢复到“健康”状态：phorpol -12-肉豆蔻酸-13-乙酸盐诱导蛋白1 （PMAIP1）、氢电压门控通道1 （HVCN1）和β-抑制蛋白1 （ARRB1）。这些基因在治疗后的上调被实时PCR证实。在气道中性粒细胞中，1029个基因在治疗后与治疗前差异表达。其中，抗生素治疗后30个基因上调，75个基因下调。然而，生物学上的合理性决定了只有下调的基因属于研究血液中性粒细胞的基因类别。最后，我们观察到，在治疗前后，常见表达的基因在气道中性粒细胞中比在血液中性粒细胞中表现出更大的变异性。这些结果表明，CF患者未来干预的更具体目标包括呼吸爆发、细胞凋亡和颗粒胞吐。
In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to “healthy” condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and after therapy. These results indicate more specific targets for future interventions in CF patients involving respiratory burst, apoptosis, and granule exocytosis.
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影响因子：
3.1
作者：
Downey, Damian G.;Brockbank, Simon;Elborn, J. Stuart
通讯作者：
Elborn, J. Stuart
DOI：
10.1186/1710-1492-2-3-98
发表时间：
2006-09-15
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Lacy P
通讯作者：
Lacy P
影响因子：
2.8
作者：
Fr端hwirth, M;Ruedl, C;Wolf, H
通讯作者：
Wolf, H
影响因子：
3.1
作者：
Levy, Hara;Kalish, Leslie A.;Weiss, Scott T.
通讯作者：
Weiss, Scott T.
影响因子：
10
作者：
Horsley, Alex R.;Davies, Jane C.;Alton, Eric W. F. W.
通讯作者：
Alton, Eric W. F. W.