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- Title
Lipoteichoic acid upregulates plasminogen activator inhibitor-1 expression in parapneumonic effusions.
- Authors
Lee, Kai‐Ling; Chen, Wei‐Lin; Chen, Ray‐Jade; Lai, Kevin S.; Chung, Chi‐Li
- Abstract
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.
- Subjects
GRAM-positive bacteria; PLASMINOGEN activator inhibitors; GENE expression; TOLL-like receptors; MESOTHELIUM
- Publication
Respirology, 2018, Vol 23, Issue 1, p89
- ISSN
1323-7799
- Publication type
Article
- DOI
10.1111/resp.13148