Erpenbeck Veit J, Hagenberg Andreas, Krentel Harald, Discher Marc, Braun Armin, Hohlfeld Jens M, Krug Norbert
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Int Arch Allergy Immunol. 2006;139(4):306-16. doi: 10.1159/000091602. Epub 2006 Feb 22.
GATA-3 (GATA binding protein 3) and the proto-oncogene c-maf are Th2-regulating transcription factors that control the expression of interleukin (IL)-4 and IL-5, while T-bet (T-box expressed in T cells) is a Th1-specific transcription factor that controls the expression of interferon (IFN-gamma). Allergen provocation in asthmatics induces a Th2-dominated cytokine profile, but so far it is unknown whether the skewed cytokine expression is reflected by the expression of the respective transcriptional regulators.
The aim of this study was to determine the regulation of Th1- and Th2-specific transcription factors and cytokines in 10 atopic subjects with mild asthma and 5 nonatopic healthy controls at baseline and after segmental sham and allergen challenge.
The mRNA expression of GATA-3, c-maf and T-bet was determined by real-time polymerase chain reaction in bronchoalveolar lavage (BAL) cells and bronchial biopsies. The percentage of IL-4+, IL-5+ and IFN-gamma+ BAL T cells was determined by flow cytometry, and BAL levels of these cytokines were measured by ELISA.
In BAL cells of asthmatics, the mRNA expression of all transcription factors was increased after allergen challenge. In bronchial biopsies, the basal expression of GATA-3 was increased in asthmatics compared to healthy controls but decreased after allergen challenge. Compared to sham challenge, the percentage of IL-5+/CD4+ BAL T cells was increased after allergen challenge in asthmatics while the percentage of IFN-gamma+/CD4+ and IFN-gamma+/CD8+ T cells was decreased. Expression of c-maf mRNA in BAL cells correlated with IL-4+/CD4+ BAL cells and BAL IL-5 levels.
Segmental allergen challenge in asthmatics leads to increased GATA-3, c-maf and T-bet expression in BAL cells but not in bronchial biopsies.
GATA-3（GATA结合蛋白3）和原癌基因c-maf是调控Th2的转录因子，可控制白细胞介素（IL）-4和IL-5的表达，而T-bet（T细胞中表达的T盒）是Th1特异性转录因子，可控制干扰素（IFN）-γ的表达。哮喘患者的变应原激发可诱导以Th2为主的细胞因子谱，但迄今为止，尚不清楚细胞因子表达的偏差是否由各自转录调节因子的表达所反映。
本研究旨在确定10名轻度哮喘特应性受试者和5名非特应性健康对照在基线时以及节段性假激发和变应原激发后的Th1和Th2特异性转录因子及细胞因子的调控情况。
通过实时聚合酶链反应测定支气管肺泡灌洗（BAL）细胞和支气管活检组织中GATA-3、c-maf和T-bet的mRNA表达。通过流式细胞术测定IL-4+、IL-5+和IFN-γ+BAL T细胞的百分比，并通过酶联免疫吸附测定法测量这些细胞因子的BAL水平。
在哮喘患者的BAL细胞中，变应原激发后所有转录因子的mRNA表达均增加。在支气管活检组织中，与健康对照相比，哮喘患者GATA-3的基础表达增加，但变应原激发后降低。与假激发相比，哮喘患者变应原激发后BAL中IL-5+/CD4+T细胞的百分比增加，而IFN-γ+/CD4+和IFN-γ+/CD8+T细胞的百分比降低。BAL细胞中c-maf mRNA的表达与IL-4+/CD4+BAL细胞及BAL中IL-5水平相关。
哮喘患者节段性变应原激发导致BAL细胞中GATA-3、c-maf和T-bet表达增加，但支气管活检组织中未增加。
