title: Molecular mechanisms of lipopolysaccharide-caused induction of surfactant protein-A gene expression in human alveolar epithelial A549 cells.
abstract: 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 LPS 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 (si)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 LPS selectively induces SP-A gene expression possibly through TLR2-mediated activation of c-Jun in human alveolar epithelial A549 cells.
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Chuang
authors.forename: Ta-Liang
authors.initials: TL
authors.lastname: Chen
authors.forename: Ruei-Ming
authors.initials: RM
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000280:Administration, Inhalation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis* / Q000235:genetics; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D007507:Therapeutic Irrigation; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000199:Actins; D008070:Lipopolysaccharides; D016755:Proto-Oncogene Proteins c-jun; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2