Augmentation of Pulmonary Epithelial Cell IL-8 Expression and Permeability by Pre-B-cell Colony Enhancing Factor.
Augmentation of Pulmonary Epithelial Cell IL-8 Expression and Permeability by Pre-B-cell Colony Enhancing Factor.
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前 B 细胞集落增强因子增强肺上皮细胞 IL-8 表达和通透性
DOI：
10.1186/1476-9255-5-15
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发表时间：
2008-09-22
期刊：
影响因子：
--
通讯作者：
Ye SQ
中科院分区：
文献类型：
--
作者：
Li H;Liu P;Cepeda J;Fang D;Easley RB;Simon BA;Zhang LQ;Ye SQ
本实验室先前的研究已将前B细胞集落增强因子（PBEF）确定为急性肺损伤（ALI）的一种新生物标志物。PBEF参与ALI发病的分子机制尚不完全清楚。本研究探讨PBEF对肺泡上皮细胞IL-8表达和通透性的调节作用。用人PBEF cDNA或PBEF siRNA转染人肺泡上皮细胞（细胞系和原代细胞），然后在存在或不存在TNFα的情况下培养。RT-PCR和Western blotting检测PBEF和IL-8的表达。此外，通过体外细胞渗透性测定评估了PBEF表达改变对肺泡上皮和动脉内皮细胞屏障调节的变化。我们的研究结果表明，在人肺泡上皮细胞中，PBEF的过表达显著增加了基础和TNFα刺激的IL-8分泌，增加了5至10倍以上，细胞通透性增加了30%以上;用siRNA敲低PBEF表达显著抑制了基础和TNFα刺激的IL-8分泌70%，IL-8 mRNA水平降低了74%。此外，PBEF表达的敲低也显著减弱了TNFα诱导的细胞渗透性43%。在人肺动脉内皮细胞中观察到类似的结果。这些结果提示PBEF可能通过调节IL-8等炎症因子在基础和TNFα介导的肺部炎症和肺上皮屏障功能障碍中发挥重要作用，这可能部分解释了PBEF在ALI易感性和发病机制中的作用。这些结果进一步支持PBEF作为ALI诊断和治疗靶点的潜力。
Previous studies in our lab have identified Pre-B-cell colony enhancing factor (PBEF) as a novel biomarker in acute lung injury (ALI). The molecular mechanism of PBEF involvement in the pathogenesis of ALI is still incompletely understood. This study examined the role of PBEF in regulating pulmonary alveolar epithelial cell IL-8 expression and permeability. Human pulmonary alveolar epithelial cells (cell line and primary cells) were transfected with human PBEF cDNA or PBEF siRNA and then cultured in the presence or absence of TNFα. PBEF and IL-8 expression were analyzed by RT-PCR and Western blotting. In addition, changes in pulmonary alveolar epithelial and artery endothelial cell barrier regulation with altered PBEF expression was evaluated by an in vitro cell permeability assay. Our results demonstrated that, in human pulmonary alveolar epithelial cells, the overexpression of PBEF significantly augmented basal and TNFα-stimulated IL-8 secretion by more than 5 to 10-fold and increased cell permeability by >30%; the knockdown of PBEF expression with siRNA significantly inhibited basal and TNFα-stimulated IL-8 secretion by 70% and IL-8 mRNA levels by 74%. Further, the knockdown of PBEF expression also significantly attenuated TNFα-induced cell permeability by 43%. Similar result was observed in human pulmonary artery endothelial cells. These results suggest that PBEF may play a vital role in basal and TNFα-mediated pulmonary inflammation and pulmonary epithelial barrier dysfunction via its regulation of other inflammatory cytokines such as IL-8, which could in part explain the role of PBEF in the susceptibility and pathogenesis of ALI. These results lend further support to the potential of PBEF to serve as a diagnostic and therapeutic target to ALI.
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DOI：
10.1164/ajrccm.164.10.2104013
发表时间：
2001-11-15
影响因子：
24.7
作者：
Park, WY;Goodman, RB;Martin, TR
通讯作者：
Martin, TR
影响因子：
15.9
作者：
FOLKESSON, HG;MATTHAY, MA;BROADDUS, VC
通讯作者：
BROADDUS, VC
影响因子：
9.6
作者：
Calfee, Carolyn S.;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
DOI：
10.1084/jem.167.6.1883
发表时间：
1988-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsushima K;Morishita K;Yoshimura T;Lavu S;Kobayashi Y;Lew W;Appella E;Kung HF;Leonard EJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
DOI：
10.1164/rccm.200208-966ws
发表时间：
2003-04-01
影响因子：
24.7
作者：
Matthay, MA;Zimmerman, GA;Harabin, AL
通讯作者：
Harabin, AL