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红霉素对人胸膜间皮细胞活力、肿瘤坏死因子-α和转化生长因子-β1分泌及连接蛋白43表达的影响。

The effects of erythromycin on the viability and the secretion of TNF-alpha and TGF-beta1 and expression of connexin43 by human pleural mesothelial cells.

作者信息

Xie Canmao, Huang Jian Qiang, Light Richard W

机构信息

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhongshan (Sun Yat-sen) University, Guangzhou, China.

出版信息

Respirology. 2005 Nov;10(5):567-71. doi: 10.1111/j.1440-1843.2005.00751.x.

DOI:10.1111/j.1440-1843.2005.00751.x
PMID:16268908
Abstract

OBJECTIVE

The mechanism by which erythromycin produces pleurodesis remains unknown. The purpose of this study was to investigate the effects of erythromycin on human pleural mesothelial cell (HPMC) viability, the secretion of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1) (TGF-beta(1)) and the level of expression of connexin43.

METHODOLOGY

HPMC were incubated with different concentrations of erythromycin. The inhibitory effects of erythromycin on HPMC growth were measured using a tetrazolium-based colorimetric assay. The levels of TNF-alpha and TGF-beta(1) in supernatants were measured by ELISA and levels of connexin43 were assessed by Western blot.

RESULTS

Erythromycin injured HPMC in a dose and time-dependent manner. The secretion of both TNF-alpha and TGF-beta(1) by HMPC increased significantly when they were incubated with 100 mg/L erythromycin for 3 or 5 days. The levels of connexin43 in HPMC decreased after incubation with 100 mg/L erythromycin and no relationship was observed between the levels and incubation time.

CONCLUSIONS

Erythromycin injures HPMC in a dose- and time-dependent manner and results in the secretion of TNF-alpha and TGF-beta(1). This is one possible mechanism of pleurodesis with erythromycin. Furthermore, erythromycin decreased the levels of connexin43 in HPMC, which could possibly affect the response of HPMC to pleurodesis with erythromycin.

摘要

目的

红霉素产生胸膜固定术的机制尚不清楚。本研究的目的是探讨红霉素对人胸膜间皮细胞(HPMC)活力、肿瘤坏死因子-α(TNF-α)和转化生长因子-β1(TGF-β1)分泌以及连接蛋白43表达水平的影响。

方法

将HPMC与不同浓度的红霉素孵育。采用基于四氮唑的比色法测定红霉素对HPMC生长的抑制作用。通过酶联免疫吸附测定法(ELISA)测量上清液中TNF-α和TGF-β1的水平,并通过蛋白质印迹法评估连接蛋白43的水平。

结果

红霉素以剂量和时间依赖性方式损伤HPMC。当HMPC与100mg/L红霉素孵育3天或5天时,TNF-α和TGF-β1的分泌均显著增加。与100mg/L红霉素孵育后,HPMC中连接蛋白43的水平降低,且未观察到该水平与孵育时间之间的关系。

结论

红霉素以剂量和时间依赖性方式损伤HPMC,并导致TNF-α和TGF-β1的分泌。这是红霉素胸膜固定术的一种可能机制。此外,红霉素降低了HPMC中连接蛋白43的水平,这可能会影响HPMC对红霉素胸膜固定术的反应。

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