Molecular mechanisms of lipopolysaccharide-caused induction of surfactant protein-A gene expression in human alveolar epithelial A549 cells
Molecular mechanisms of lipopolysaccharide-caused induction of surfactant protein-A gene expression in human alveolar epithelial A549 cells
复制标题
DOI：
10.1016/j.toxlet.2009.08.015
复制
发表时间：
2009-12-15
影响因子：
3.5
通讯作者：
Chen, Ruei-Ming
中科院分区：
文献类型：
--
作者：
Chuang, Chi-Yuan;Chen, Ta-Liang;Chen, Ruei-Ming
表面活性蛋白（SP）参与脓毒症引起的急性肺损伤的生理和病理生理调节。脂多糖（LPS），一种革兰氏阴性细菌外膜成分。是感染性休克的主要原因之一。本研究旨在评估LPS对人肺泡上皮A549细胞SP-A和SP-D基因表达的调节作用。将 A549 细胞暴露于 LIPS 会以浓度和时间依赖性方式增加 SP-A mRNA 的合成，而不影响 SP-D mRNA 的产生。 LPS 选择性增强转录因子 c-Jun 从细胞质到细胞核的易位，但不增强核因子 kappa-B。同时，LPS 增加了 AP-1 的 DNA 结合活性，用 c-Jun N 末端激酶抑制剂 SP600125 预处理 A549 细胞，减少了 c-Jun 易位，并显着改善了 LPS 诱导的 SP-A mRNA 产生。 LPS 处理后，A549 细胞中 Toll 样受体 (TLR2) mRNA 水平呈时间依赖性诱导。将 TLR2 小干扰 (s1)RNA 应用于 A549 细胞，显着降低该受体的翻译，同时减轻 LPS 诱导的 SP-A 合成。综上所述，本研究表明，LIPS 可能通过人肺泡上皮 A549 中 TLR2 介导的 c-Jun 激活选择性诱导 SP-A 基因表达细胞。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Surfactant proteins (SPs) participate in the physiological and pathophysiological regulation of sepsis-induced acute lung injury. Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component. is one of the major causes of septic shock. This study was designed to evaluate the effects of LPS on the regulation of SP-A and SP-D gene expressions in human alveolar epithelial A549 cells. Exposure of A549 cells to LIPS increased SP-A mRNA synthesis in concentration and time-dependent manners without affecting SP-D mRNA production. LPS selectively enhanced translocation of transcription factor c-Jun from the cytoplasm to nuclei, but not nuclear factor kappa-B. In parallel, the DNA-binding activity of AP-1 was increased by LPS, Pretreatment of A549 cells with SP600125, an inhibitor of c-Jun N-terminal kinase, decreased c-Jun translocation, and significantly ameliorated LPS-induced SP-A mRNA production. Levels of toll-like receptor (TLR2) mRNA in A549 cells were time-dependently induced following LPS treatment Application of TLR2 small interference (s1)RNA into A549 cells significantly knocked-down the translation of this receptor, and simultaneously alleviated LPS-induced SP-A synthesis Taken together, this study has shown that LIPS selectively induces SP-A gene expression possibly through TLR2-mediated activation of c-Jun in human alveolar epithelial A549 cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.