Abstract

Background and objective: Parapneumonic effusion (PPE) is commonly caused by Gram-positive bacteria (GPB) and often presents with pleural loculation, which is characterized by overproduction of plasminogen activator inhibitor (PAI)-1. Lipoteichoic acid (LTA), a surface adhesion molecule of GPB, binds to the pleural mesothelium and triggers inflammation. However, the effects of LTA on PAI-1 expression in PPE and underlying mechanisms remain unclear. Methods: Thirty consecutive patients with PPE were enrolled, including uncomplicated culture negative (CN, n = 11), Gram-negative bacteria (GNB, n = 7) and GPB (n = 12) groups stratified by pleural fluid characteristics and bacteriology, and the effusion PAI-1 levels were measured. In addition, human pleural mesothelial cells (PMC) were treated with LTA and the expression of PAI-1 and activation of signalling pathways were assayed. Results: The median levels of PAI-1 were significantly higher in GPB (160.5 ng/mL) and GNB (117.0 ng/mL) groups than in the uncomplicated CN (58.0 ng/mL) group. In human PMC, LTA markedly upregulated PAI-1 mRNA and protein expression and enhanced elaboration of Toll-like receptor 2 (TLR2). Furthermore, LTA increased c-Jun N-terminal kinase (JNK) phosphorylation, induced activating transcription factor 2 (ATF2)/c-Jun nuclear translocation and activated PAI-1 promoter activity. Pretreatment with TLR2 siRNA significantly inhibited LTA-induced JNK phosphorylation and PAI-1 protein expression. Conclusion: Culture-positive PPE, especially that caused by GPB, has a significantly higher level of PAI-1 than uncomplicated CN PPE. LTA upregulates PAI-1 expression through activation of TLR2/JNK/activator protein 1 (AP-1) pathway in human PMC. Better understanding of the modulation of PAI-1 synthesis by LTA in PPE may provide potential therapies for infected pleural effusions.

Original languageEnglish
Pages (from-to)89-95
Number of pages7
JournalRespirology
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • lipoteichoic acid
  • parapneumonic effusion
  • plasminogen activator inhibitor
  • pleural mesothelial cell
  • Toll-like receptor
  • Up-Regulation/drug effects
  • Plasminogen Activator Inhibitor 1/genetics
  • Humans
  • Middle Aged
  • Male
  • Pleural Effusion/metabolism
  • Aged, 80 and over
  • Adult
  • Female
  • Cell Culture Techniques
  • Pleura/cytology
  • Epithelial Cells/metabolism
  • Activating Transcription Factor 2/metabolism
  • Gram-Negative Bacteria
  • JNK Mitogen-Activated Protein Kinases/metabolism
  • Lipopolysaccharides/pharmacology
  • Gram-Positive Bacteria
  • Teichoic Acids/pharmacology
  • Toll-Like Receptor 2/genetics
  • Signal Transduction/drug effects
  • RNA, Messenger/metabolism
  • Transcription Factor AP-1/metabolism
  • Aged
  • Phosphorylation/drug effects

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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