Toll-like receptor 2-mediated sequential activation of MyD88 and MAPKs contributes to lipopolysaccharide-induced sp-a gene expression in human alveolar epithelial cells

被引:12
作者
Chuang, Chi-Yuan [2 ,3 ]
Chen, Tyng-Guey [4 ]
Tai, Yu-Tyng [4 ]
Chen, Ta-Liang [2 ]
Lin, Yu-Hua [2 ]
Tsai, Cheng Hsiu
Chen, Ruei-Ming [1 ,5 ]
机构
[1] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei 110, Taiwan
[2] Taipei Med Univ, Grad Inst Clin Med, Taipei 110, Taiwan
[3] Taipei City Hosp, Dept Pulmonol, Div Internal Med, Ren Ai Branch, Taipei, Taiwan
[4] Taipei Med Univ, Wan Fang Hosp, Dept Anesthesiol, Taipei 110, Taiwan
[5] Taipei Med Univ, Wan Fang Hosp, Drug Abuse Res Ctr, Taipei 110, Taiwan
关键词
Acute lung injury; Alveolar epithelial cells; Lipopolysaccharide; MyD88-MEK4-JNK1-AP-1; Surfactant protein-A; Toll-like receptor 2; SURFACTANT PROTEIN-A; KINASE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; C-JUN; LUNG; MACROPHAGES; RESPONSES; PATHWAYS; LPS;
D O I
10.1016/j.imbio.2010.10.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Surfactant proteins (SPs) produced by pulmonary epithelial cells participate in the regulation of sepsisinduced acute lung injury. Our previous study has shown that lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, can regulate sp-a gene expression in human lung carcinoma type II epithelial A549 cells. This study was further designed to evaluate the signal-transducing mechanisms of LPS-induced sp-a gene expression. Exposure of A549 cells to LPS induced SP-A mRNA and protein production in time-dependent manners. Application of toll-like receptor 2 (TLR2) siRNA into A549 cells decreased the levels of this receptor and simultaneously inhibited LPS-induced SP-A mRNA expression. Sequentially, LPS enhanced phosphorylation of mitogen-activated protein kinase (MEK) 4 and c-Jun NH2 terminal kinase 1 (JNK1) in time-dependent manners. Application of TLR2 siRNA decreased LPS-enhanced phosphorylation of MEK4 and JNK1. After knocking-down the translation of MyD88 by RNA interference, the LPS-triggered MEK4 phosphorylation was attenuated. Consequently, LPS augmented the translocation of c-Jun from the cytoplasm to nuclei without affecting c-Fos. Pretreatment of A549 cells with SP600125, an inhibitor of JNK1, significantly lowered LPS-induced SP-A mRNA production. Analyses of an electrophoretic mobility shift assay and a reporter gene further showed that LPS increased the transactivation activity of AP-1 in A549 cells. Therefore, the present study demonstrates that LPS can induce sp-a gene expression in human type II epithelial A549 cells through TLR2-mediated sequential activation of MyD88-MEK4-JNK1-AP-1. (C) 2010 Elsevier GmbH. All rights reserved.
引用
收藏
页码:707 / 714
页数:8
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