The Effect of Tissue Plasminogen Activator on TGF-beta1 Pre-Treated Human Mesothelial Cell Line.
10.4046/trd.2011.70.5.405
- Author:
Junglim LEE
1
;
Soo Jin JEON
;
Young Choon YOO
;
Ji Hye KIM
;
Yu Mi LEE
;
Sun Jung KWON
;
Ji Woong SON
;
Eugene CHOI
;
Moon Jun NA
Author Information
1. Department of Microbiology, Konyang University College of Medicine, Daejeon, Korea.
- Publication Type:Original Article
- Keywords:
Humans;
Mesothelium;
Cell Line;
Tissue Plasminogen Activator;
Transforming Growth Factor;
Collagen
- MeSH:
Cell Line;
Cell Survival;
Collagen;
Collagen Type I;
Doxycycline;
Empyema;
Enzyme-Linked Immunosorbent Assay;
Epithelium;
Fibrosis;
Humans;
Interleukin-8;
Interleukins;
Real-Time Polymerase Chain Reaction;
RNA, Messenger;
Talc;
Tissue Plasminogen Activator;
Transforming Growth Factor beta1;
Transforming Growth Factors;
Vascular Endothelial Growth Factor A
- From:Tuberculosis and Respiratory Diseases
2011;70(5):405-415
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: In an effort to find alternative therapeutic agents to prevent excessive fibrosis as a sequela to complicated parapneumonic effusion or empyema, we examined the effect of tissue plasminogen activator (tPA) as a fibrinolytic agent combined with talc or transforming growth factor (TGF)-beta1 in a human pleural mesothelial cell line, MeT-5A. METHODS: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-beta1 for 24 h and then were treated with tPA for an additional 24 h. Cell viability was measured by MTT assay. The production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in the culture supernatants was measured by ELISA. Real-time PCR was carried out for measurement of type I collagen mRNA. RESULTS: MeT-5A cells treated with talc showed a dose-dependent increase in production of IL-8. Talc also increased production of type I collagen mRNA at low doses, but talc did not influence the induction of VEGF. Addition of tPA to talc-stimulated cells showed further increases in the production of IL-8, but tPA did not influence the production of VEGF or type I collagen mRNA. TGF-beta1 increased the production of both VEGF and collagen type I mRNA, both of which were effectively inhibited by additional tPA treatment in MeT-5A cells. CONCLUSION: TGF-beta1 is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition of tPA after TGF-beta1 stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production.
