Arnold Ralf, König Wolfgang
Institute of Medical Microbiology, Otto-von-Guericke-University, Leipzigerstr. 44, 39120 Magdeburg, Germany.
Virology. 2006 Mar 15;346(2):427-39. doi: 10.1016/j.virol.2005.11.009. Epub 2005 Dec 5.
The epithelial cells of the airways are the target cells for respiratory syncytial virus (RSV) infection and the site of the majority of the inflammation associated with the disease. Recently, peroxisome-proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily, has been shown to possess anti-inflammatory properties. Therefore, we investigated the role of PPARgamma agonists (15d-PGJ(2), ciglitazone and troglitazone) on the synthesis of RSV-induced cytokine release from RSV-infected human lung epithelial cells (A549). We observed that all PPARgamma ligands inhibited dose-dependently the release of TNF-alpha, GM-CSF, IL-1alpha, IL-6 and the chemokines CXCL8 (IL-8) and CCL5 (RANTES) from RSV-infected A549 cells. Concomitantly, the PPARgamma ligands diminished the cellular amount of mRNA encoding for IL-6, CXCL8 and CCL5 and the RSV-induced binding activity of the transcription factors NF-kappaB (p65/p50) and AP-1 (c-fos), respectively. Our data presented herein suggest a potential application of PPARgamma ligands in the anti-inflammatory treatment of RSV infection.
气道上皮细胞是呼吸道合胞病毒（RSV）感染的靶细胞，也是与该疾病相关的大部分炎症反应发生的部位。最近，核激素受体超家族成员过氧化物酶体增殖物激活受体γ（PPARγ）已被证明具有抗炎特性。因此，我们研究了PPARγ激动剂（15d-PGJ₂、西格列他唑和曲格列酮）对RSV感染的人肺上皮细胞（A549）中RSV诱导的细胞因子释放合成的作用。我们观察到，所有PPARγ配体均剂量依赖性地抑制了RSV感染的A549细胞中TNF-α、GM-CSF、IL-1α、IL-6以及趋化因子CXCL8（IL-8）和CCL5（RANTES）的释放。同时，PPARγ配体分别减少了编码IL-6、CXCL8和CCL5的mRNA的细胞含量以及RSV诱导的转录因子NF-κB（p65/p50）和AP-1（c-fos）的结合活性。本文提供的数据表明PPARγ配体在RSV感染的抗炎治疗中具有潜在应用价值。
