Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases....Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in E/f3 (homologous to human ESE-1) knockout mice, the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.展开更多
细菌溶解产物(bacterial lysates,BLs)是近年兴起的一种免疫调节剂,它可以通过调节体内的免疫系统从而增强机体的抗感染能力。BLs还可以通过改变辅助性T细胞(help T cell,Th)1/Th2平衡降低变态反应的发生率。以往关于BLs的研究主要集中...细菌溶解产物(bacterial lysates,BLs)是近年兴起的一种免疫调节剂,它可以通过调节体内的免疫系统从而增强机体的抗感染能力。BLs还可以通过改变辅助性T细胞(help T cell,Th)1/Th2平衡降低变态反应的发生率。以往关于BLs的研究主要集中在预防儿童和成人反复呼吸道感染中,近些年在变应性疾病中的应用逐渐增多。文章就BLs在变应性气道疾病中的作用机制及最新研究进展进行综述。展开更多
文摘Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in E/f3 (homologous to human ESE-1) knockout mice, the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.
文摘细菌溶解产物(bacterial lysates,BLs)是近年兴起的一种免疫调节剂,它可以通过调节体内的免疫系统从而增强机体的抗感染能力。BLs还可以通过改变辅助性T细胞(help T cell,Th)1/Th2平衡降低变态反应的发生率。以往关于BLs的研究主要集中在预防儿童和成人反复呼吸道感染中,近些年在变应性疾病中的应用逐渐增多。文章就BLs在变应性气道疾病中的作用机制及最新研究进展进行综述。