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.
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.


METHODS
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.
Xie
Canmao
C
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhongshan (Sun Yat-sen) University, Guangzhou, China.
Huang
Jian Qiang
JQ
Light
Richard W
RW
D000704:Analysis of Variance; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D010994:Pleura / Q000166:cytology; D018700:Pleurodesis; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D018031:Connexin 43; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D004917:Erythromycin