Neutrophils augment LPS-mediated pro-inflammatory signaling in human lung epithelial cells

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• 作者：Agnes W. Boots^a ; ^b ; Kirsten Gerloff^a ; Roger Bartholomé ; ^a ; Damien van Berlo^a ; Kirstin Ledermann^a ; Guido R.M.M. Haenen^b ; Aalt Bast^b ; Frederik-Jan van Schooten^a ; Catrin Albrecht^a ; Roel P.F. Schins^a ; ^{roel.schins@uni-duesseldorf.de}
• 关键词：BEAS-2B ; human bronchial epithelial cultured cell line ; CPH ; 1-hydroxy-3-carboxy-2 ; 2 ; 5 ; 5-tetramethylpyrrolidine ; DUOX1/2 ; dual oxidases 1 and 2 ; EPR ; electron paramagnetic resonance ; ERK1/2 ; extracellular signal-regulated kinases 1/2 ; H2O2 ; hydrogen perox
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2012
• 期刊代码：20_01674889
• 类别：bio
• 出版时间：July, 2012
• 卷：1823
• 期：7
• 页码：1151-1162
• 文件大小：1259 K

摘要

Background

The role of polymorphonuclear neutrophils in pulmonary host defense is well recognized. The influence of a pre-existing inflammation driven by neutrophils (neutrophilic inflammation) on the airway epithelial response toward pro-inflammatory exogenous triggers, however, is still poorly addressed. Therefore, the aim of the present study is to investigate the effect of neutrophils on lipopolysaccharide (LPS)-induced pro-inflammatory signaling in lung epithelial cells. Additionally, underlying signaling pathways are examined.

Methods

Human bronchial epithelial cells (BEAS-2B) were co-incubated with human peripheral blood neutrophils or bone-marrow derived neutrophils from either C57BL/6J wild type or nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase deficient (p47^{phox鈭?鈭?/sup>) mice. Upon stimulation with LPS, interleukin (IL)-8 production and reactive oxygen species (ROS) generation were measured. Additionally, activation of the extracellular signal-regulated kinases (ERK) 1/2 and nuclear factor (NF)-魏B signaling pathways was analyzed.}

Results

Our studies show that the presence of neutrophils synergistically increases LPS-induced IL-8 and ROS production by BEAS-2B cells without inducing cytotoxicity. The observed IL-8 response to endotoxin increases in proportion to time, LPS-concentration and the number of neutrophils present. Moreover, this synergistic IL-8 production strongly correlated with the chemotactic properties of the co-incubations and significantly depended on a functional neutrophilic NADPH oxidase. The presence of neutrophils also augments LPS-induced phosphorylation of ERK1/2 and I魏B伪 as well as NF-魏B RelA DNA binding activity in BEAS-2B cells.

Conclusions

Our results indicate that the pro-inflammatory effects of LPS toward lung epithelial cells are amplified during a pre-existing neutrophilic inflammation. These findings support the concept that patients suffering from pulmonary neutrophilic inflammation are more susceptible toward exogenous pro-inflammatory triggers.