中华医学杂志（英文版）2003，Vol.116Issue(8)：1257-1261,5.
Pro-apoptotic role of NF-κB pathway inhibition in lipopolysaccharide-stimulated polymorphonuclear neutrophils
Pro-apoptotic role of NF-κB pathway inhibition in lipopolysaccharide-stimulated polymorphonuclear neutrophils
刘艳梅 1张君岚 1赵占胜 1凌亦凌2
作者信息
- 1. Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China
- 2. Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China
- 折叠
摘要
Abstract
Objective To investigate the role of nuclear factor kappa B (NF-κB) pathway inhibition in lipopolysaccharide (LPS)-stimulated apoptosis of polymorphonuclear neutrophils (PMNs).Methods Rats with acute lung injury induced by LPS intratracheal instillation and cultured human venous PMNs were studied. Pyrrolidine dithiocarbamate (PDTC) and gliotoxin were used as NF-κB inhibitors. Additionally, to explore the role of extracellularly regulated protein kinase as an upstream signal in NF-κB pathway on regulating LPS-stimulated PMN apoptosis, PD098059, the specific inhibitor of extracellularly regulated protein kinase, was also applied. The lung injury was determined by protein content and PMN numbers in bronchoalveolar lavage fluid. PMN apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) end labeling and DNA fragmentation. IκBα degradation was analyzed by Western blot. NF-κB DNA binding activity was detected by an electrophoretic mobility shift assay.Results (1) The increase of protein content and PMN numbers in bronchoalveolar lavage fluid induced by LPS (100 μg per rat) intratracheal instillation were alleviated by PDTC (50, 100, or 200 mg/kg, I.p.) in a dose-dependent manner. (2) PMNs apoptosis in vivo or in vitro was delayed by LPS, and accelerated by PDTC, gliotoxin or PD098059 pretreatment. (3) IκBα degradation and increased NF-κB DNA binding activity mediated by LPS were inhibited by PDTC, gliotoxin or PD098059 pretreatment.Conclusion Inhibition of either NF-κB itself or the upstream signals in NF-κB pathway such as extracellularly regulated protein kinases has therapeutic effect on LPS-induced acute lung injury, in which the dysregulation of PMN apoptosis plays an important role.关键词
NF-kappa B/apoptosis/neutrophil/lipopoly-saccharidesKey words
NF-kappa B/apoptosis/neutrophil/lipopoly-saccharides分类
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刘艳梅,张君岚,赵占胜,凌亦凌..Pro-apoptotic role of NF-κB pathway inhibition in lipopolysaccharide-stimulated polymorphonuclear neutrophils[J].中华医学杂志（英文版）,2003,116(8):1257-1261,5.
