TGF-β1으로 자극한 사람중피세포주에서 조직플라스미노겐 활성제가 미치는 영향

• Published in: Tuberculosis and respiratory diseases Vol. 70; no. 5; pp. 405 - 415
• Main Authors: 이정림, Jung Lim Lee, 전수진, Soo Jin Jeon, 유영춘, Young Choon Yoo, 김지혜, Ji Hye Kim, 이유미, Yu Mi Lee, 권선중, Sun Jung Kwon, 손지웅, Ji Woong Son, 최유진, Eu Gene Choi, 나문준, Moon Jun Na
• Format: Journal Article
• Language: Korean
• Published: 대한결핵 및 호흡기학회 30.05.2011; 대한결핵및호흡기학회
• Subjects: Cell Line; Collagen; Humans; Mesothelium; Tissue Plasminogen Activator; Transforming Growth Factor; 내과학
• ISSN: 1738-3536; 2005-6184

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.