Canmao Xie1, Jian Qiang Huang, Richard W Light. 1. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhongshan (Sun Yat-sen) University, Guangzhou, China.
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.
OBJECTIVE: The mechanism by which erythromycin produces pleurodesis remains unknown. The purpose of this study was to investigate the effects of erythromycin on humanpleural 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.
Authors: Haining Yang; Maurizio Bocchetta; Barbara Kroczynska; Amira G Elmishad; Yuanbin Chen; Zemin Liu; Concetta Bubici; Brooke T Mossman; Harvey I Pass; Joseph R Testa; Guido Franzoso; Michele Carbone Journal: Proc Natl Acad Sci U S A Date: 2006-06-23 Impact factor: 11.205