title: Lipopolysaccharide stimulates syntheses of toll-like receptor 2 and surfactant protein-A in human alveolar epithelial A549 cells through upregulating phosphorylation of MEK1 and ERK1/2 and sequential activation of NF-κB.
abstract: Surfactant proteins (SPs) and toll-like receptors (TLRs) contribute to regulation of sepsis-induced acute lung injury. Lipopolysaccharide (LPS) is one of the major causes of septic shock. This study was designed to evaluate the effects of LPS on the regulation of tlr-2 and sp-a gene expression in human alveolar epithelial A549 cells and the possible mechanisms. Exposure of A549 cells to LPS increased the expressions of TLR2 and SP-A mRNA and protein in time-dependent manners. A search using a bioinformatic approach found that there are several nuclear factor kappa-B (NF-κB)-DNA-binding motifs in the promoter region of the tlr2 and sp-a genes. Immunoblotting analyses revealed that exposure to LPS time-dependently enhanced the translocation of NF-κB from the cytoplasm to nuclei. Analyses of an electrophoretic mobility shift assay further showed that LPS augmented the transactivation activity of NF-κB to its consensus oligonucleotides in A549cells. Sequentially, treatment of A549 cells with LPS increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38-mitogen-activated protein kinase (p38MAPK), and MAPK kinase-1 (MEK1). Pretreatment with PD98059, an inhibitor of ERK1/2, significantly decreased LPS-induced TLR2 and SP-A mRNA expression.
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tsu-Tuan
authors.initials: TT
authors.lastname: Wu
authors.forename: Ta-Liang
authors.initials: TL
authors.lastname: Chen
authors.forename: Wun-Sing
authors.initials: WS
authors.lastname: Loon
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tai
authors.forename: Yih-Giun
authors.initials: YG
authors.lastname: Cherng
authors.forename: Ruei-Ming
authors.initials: RM
authors.lastname: Chen
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; C445842:SFTPA1 protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one