title: Lipidome and transcriptome profiling of pneumolysin intoxication identifies networks involved in statin-conferred protection of airway epithelial cells.
abstract: Pneumonia remains one of the leading causes of death in both adults and children worldwide. Despite the adoption of a wide variety of therapeutics, the mortality from community-acquired pneumonia has remained relatively constant. Although viral and fungal acute airway infections can result in pneumonia, bacteria are the most common cause of community-acquired pneumonia, with Streptococcus pneumoniae isolated in nearly 50% of cases. Pneumolysin is a cholesterol-dependent cytolysin or pore-forming toxin produced by Streptococcus pneumonia and has been shown to play a critical role in bacterial pathogenesis. Airway epithelium is the initial site of many bacterial contacts and its barrier and mucosal immunity functions are central to infectious lung diseases. In our studies, we have shown that the prior exposure to statins confers significant resistance of airway epithelial cells to the cytotoxicity of pneumolysin. We decided to take this study one step further, assessing changes in both the transcriptome and lipidome of human airway epithelial cells exposed to toxin, statin or both. Our current work provides the first global view in human airway epithelial cells of both the transcriptome and the lipid interactions that result in cellular protection from pneumolysin.
authors.affiliation: Center for Comparative Respiratory Biology and Medicine, University of California at Davis, Davis 95616 California.
authors.forename: Sarah
authors.initials: S
authors.lastname: Statt
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Jhen-Wei
authors.initials: JW
authors.lastname: Ruan
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
authors.forename: Chih-Ting
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Center for Comparative Respiratory Biology and Medicine, University of California at Davis, Davis 95616 California.
authors.forename: Reen
authors.initials: R
authors.lastname: Wu
authors.affiliation: 1] Center for Comparative Respiratory Biology and Medicine, University of California at Davis, Davis 95616 California [2] Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan [3] Research and Development Center for Immunology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Kao
mesh_terms: D001426:Bacterial Proteins / Q000633:toxicity; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology; D004847:Epithelial Cells; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D050356:Lipid Metabolism; D008563:Membrane Lipids / Q000378:metabolism; D055442:Metabolome; D020011:Protective Agents / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction; D013301:Streptolysins / Q000633:toxicity*; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008563:Membrane Lipids; D020011:Protective Agents; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae