Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation
Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation
复制标题
DOI：
10.1186/1465-9921-6-89
复制
发表时间：
2005-08-08
影响因子：
5.8
通讯作者：
Yang, PC
中科院分区：
文献类型：
--
作者：
Yao, PL;Tsai, MF;Yang, PC
背景资料：茶碱作为支气管扩张剂已被广泛用于治疗支气管哮喘，并被认为可调节免疫反应。虽然巨噬细胞在哮喘中的重要性已被重新评价和强调，但其意义尚未得到充分研究。我们进行了一个全基因组的基因表达谱的巨噬细胞在响应theophylline.Methods：微阵列技术被用来描绘的基因表达模式的茶碱调制的巨噬细胞。采用北方杂交和实时荧光定量RT-PCR验证芯片结果，Western blot和ELISA检测IL-13和LTC 4表达水平。结果：筛选出茶碱剂量依赖性下调或上调巨噬细胞中的数十个基因。这些基因包括与炎症、细胞因子、信号转导、细胞粘附和运动、细胞周期调节因子和代谢相关的基因。我们观察到，IL-13，气道炎症的中央介质，显着抑制茶碱。实时定量RT-PCR和ELISA分析也证实了这些结果，不考虑PMA处理的THP-1细胞或分离的人肺泡巨噬细胞。茶碱、咯利普兰、依他唑酯、db-cAMP和forskolin均抑制IL-13 mRNA表达（分别为25%、2.73%、8.12%、5.28%和18.41%）和蛋白分泌（分别为2.73%、8.12%、5.28%和18.41%）。
Background: Theophylline has been used widely as a bronchodilator for the treatment of bronchial asthma and has been suggested to modulate immune response. While the importance of macrophages in asthma has been reappraised and emphasized, their significance has not been well investigated. We conducted a genome-wide profiling of the gene expressions of macrophages in response to theophylline.Methods: Microarray technology was used to profile the gene expression patterns of macrophages modulated by theophylline. Northern blot and real-time quantitative RT-PCR were also used to validate the microarray data, while Western blot and ELISA were used to measure the levels of IL-13 and LTC4.Results: We identified dozens of genes in macrophages that were dose-dependently down- or up-regulated by theophylline. These included genes related to inflammation, cytokines, signaling transduction, cell adhesion and motility, cell cycle regulators, and metabolism. We observed that IL-13, a central mediator of airway inflammation, was dramatically suppressed by theophylline. Real-time quantitative RT-PCR and ELISA analyses also confirmed these results, without respect to PMA-treated THP-1 cells or isolated human alveolar macrophages. Theophylline, rolipram, etazolate, db-cAMP and forskolin suppressed both IL-13 mRNA expression (similar to 25%, 2.73%, 8.12%, 5.28%, and 18.41%, respectively) and protein secretion (