Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
Respirology. 2018 Jan;23(1):89-95. doi: 10.1111/resp.13148. Epub 2017 Aug 23.
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.
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.
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.
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.
脓胸性胸腔积液（PPE）通常由革兰阳性菌（GPB）引起，常表现为胸腔分隔，其特征为纤溶酶原激活物抑制剂-1（PAI-1）过度产生。GPB 的表面黏附分子脂磷壁酸（LTA）与胸膜间皮结合并引发炎症。然而，LTA 对 PPE 中 PAI-1 表达的影响及其潜在机制尚不清楚。
连续纳入 30 例 PPE 患者，根据胸腔液特征和细菌学分为单纯培养阴性（CN，n=11）、革兰阴性菌（GNB，n=7）和 GPB（n=12）组，测量胸腔积液中 PAI-1 水平。此外，用人胸膜间皮细胞（PMC）处理 LTA，检测 PAI-1 的表达和信号通路的激活。
GPB（160.5ng/mL）和 GNB（117.0ng/mL）组 PAI-1 水平显著高于单纯 CN 组（58.0ng/mL）。在人 PMC 中，LTA 明显上调 PAI-1 mRNA 和蛋白表达，并增强 Toll 样受体 2（TLR2）的表达。此外，LTA 增加 c-Jun N-末端激酶（JNK）磷酸化，诱导激活转录因子 2（ATF2）/c-Jun 核转位并激活 PAI-1 启动子活性。TLR2 siRNA 预处理可显著抑制 LTA 诱导的 JNK 磷酸化和 PAI-1 蛋白表达。
培养阳性 PPE，尤其是由 GPB 引起的 PPE，其 PAI-1 水平明显高于单纯 CN PPE。LTA 通过激活人 PMC 中的 TLR2/JNK/激活蛋白 1（AP-1）通路上调 PAI-1 表达。更好地理解 LTA 在 PPE 中对 PAI-1 合成的调节可能为感染性胸腔积液提供潜在的治疗方法。
