title: Lipoteichoic acid induces surfactant protein-A biosynthesis in human alveolar type II epithelial cells through activating the MEK1/2-ERK1/2-NF-κB pathway.
abstract: BACKGROUND
  Lipoteichoic acid (LTA), a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that the gram-negative endotoxin, lipopolysaccharide (LPS), could induce surfactant protein-A (SP-A) production in human alveolar epithelial (A549) cells.
  
  
  OBJECTIVE
  In this study, we further evaluated the effect of LTA on SP-A biosynthesis and its possible signal-transducing mechanisms.
  
  
  METHODS
  A549 cells were exposed to LTA. Levels of SP-A, nuclear factor (NF)-κB, extracellular signal-regulated kinase 1/2 (ERK1/2), and mitogen-activated/extracellular signal-regulated kinase kinase (MEK)1 were determined.
  
  
  RESULTS
  Exposure of A549 cells to 10, 30, and 50 μg/ml LTA for 24 h did not affect cell viability. Meanwhile, when exposed to 30 μg/ml LTA for 1, 6, and 24 h, the biosynthesis of SP-A mRNA and protein in A549 cells significantly increased. As to the mechanism, LTA enhanced cytosolic and nuclear NF-κB levels in time-dependent manners. Pretreatment with BAY 11-7082, an inhibitor of NF-κB activation, significantly inhibited LTA-induced SP-A mRNA expression. Sequentially, LTA time-dependently augmented phosphorylation of ERK1/2. In addition, levels of phosphorylated MEK1 were augmented following treatment with LTA.
  
  
  CONCLUSIONS
  Therefore, this study showed that LTA can increase SP-A synthesis in human alveolar type II epithelial cells through sequentially activating the MEK1-ERK1/2-NF-κB-dependent pathway.
authors.affiliation: Department of Anesthesiology, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Liu
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Chuang
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tai
authors.forename: Hsiu-Lien
authors.initials: HL
authors.lastname: Tang
authors.forename: Tyng-Guey
authors.initials: TG
authors.lastname: Chen
authors.forename: Ta-Liang
authors.initials: TL
authors.lastname: Chen
authors.forename: Ruei-Ming
authors.initials: RM
authors.lastname: Chen
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013682:Teichoic Acids / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D037662:Pulmonary Surfactant-Associated Protein A; D013682:Teichoic Acids; C009900:lipoteichoic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3