Apoptosis signals in atopy and asthma measured with cDNA arrays
Apoptosis signals in atopy and asthma measured with cDNA arrays
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DOI：
10.1046/j.1365-2249.2001.01441.x
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发表时间：
2001-02-01
影响因子：
4.6
通讯作者：
Woodcock, A
中科院分区：
文献类型：
--
作者：
Brutsche, MH;Brutsche, IC;Woodcock, A
各种研究强调了控制炎性细胞寿命以及促存活和促凋亡信号传导的平衡的重要性。最近，发现哮喘与肺组织中炎性细胞凋亡减少有关。本研究的目的是利用cDNA阵列技术研究特应性和哮喘中细胞凋亡通路的系统激活。18名特应性哮喘患者（AA）、8名特应性非哮喘患者（AN）和14名健康对照者（C）被纳入本研究。用梯度离心法分离外周血单个核细胞，纯化mRNA，反转录探针与cDNA阵列杂交。通过标准化至100个最高表达的基因来比较信号，并用Mann-Whitney U检验评估组差异。我们发现了一个协同上调的几个促生存细胞因子和生长因子在AN和AA。FAS和FASL在AN和AA中无差异表达，但FAST激酶在AN和AA中过表达。肿瘤坏死因子途径在AN和AA中被激活，细胞因子和受体水平增加，TRAF 2（细胞内信号产物）增加。有迹象表明下调p53系统。相反，Bcl-2家族基因在AN和AA中表现出净促凋亡特征。半胱天冬酶组在所有组中均表现出恒定的基因表达模式。总之，哮喘相关基因的表达显着差异，发现在外周血中的特应性个体和哮喘。cDNA阵列技术被证明是有用的，可以补充DNA为基础的研究，以分析互动和多维的途径，如这里所示的细胞凋亡。
A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signalling. Recently, asthma was found to be associated with reduced apoptosis of inflammatory cells in lung tissue. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in atopy and asthma. Eighteen atopic asthmatics (AA), eight atopic non-asthmatic (AN) and 14 healthy control subjects (C) were included in the study. Peripheral blood mononuclear cells were separated with gradient centrifugation, mRNA purified and the reverse-transcribed probes hybridized to cDNA arrays. The signals were compared by standardizing to the 100 most expressed genes and group differences assessed with the Mann-Whitney U-test. We found a concerted up-regulation of several pro-survival cytokines and growth factors in AN and AA. FAS and FASL were not differentially expressed, but FAST kinase was over-expressed in AN and AA. The tumour necrosis factor pathway was activated in AN and AA with increased cytokine and receptor levels and increased TRAF2, an intracellular signalling product. There were indications of a down-regulated p53 system. In contrast, the Bcl-2 family of genes showed a net pro-apoptotic profile in AN and AA. The group of caspases showed a constant gene expression pattern in all groups. In conclusion, significant differences in the expression of apoptosis-related genes were found in peripheral blood of atopic individuals with and without asthma. cDNA array technology proved to be useful and may be complementary to DNA-based studies in order to analyse interactive and multidimensional pathways as shown here for apoptosis.