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KMID : 0383820110700050405
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Tuberculosis and Respiratory Diseases
2011 Volume.70 No. 5 p.405 ~ p.415
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The Effect of Tissue Plasminogen Activator on TGF-β1 Pre-Treated Human Mesothelial Cell Line
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Lee Jung-Lim
Jeon Soo-Jin
Yoo Young-Choon
Kim Ji-Hye
Lee Yu-Mi
Kwon Sun-Jung
Son Ji-Woong
Choi Eu-Gene
Na Moon-Jun
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Abstract
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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)-β1 in a human pleural mesothelial
cell line, MeT-5A.
Methods: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-β1 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-β1 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-β1 is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition
of tPA after TGF-β1 stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production.
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KEYWORD
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Humans, Mesothelium, Cell Line, Tissue Plasminogen Activator, Transforming Growth Factor, Collagen
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