PG490-88, a Derivative of Triptolide, Blocks Bleomycin-Induced Lung Fibrosis
In this study we evaluate the antifibrotic properties of PG-490-88, a water-soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse mode...
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Veröffentlicht in: | The American journal of pathology 2001-03, Vol.158 (3), p.997-1004 |
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Sprache: | eng |
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Zusammenfassung: | In this study we evaluate the antifibrotic properties of PG-490-88, a water-soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse model and found that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or 5 days after bleomycin. PG490-88 also markedly reduced the number of myofibroblasts in the bleomycin treatment group. An enzyme-linked immunosorbent assay of transforming growth factor (TGF)-β in the bronchoalveolar lavage fluid showed a significant decrease in TGF-β in the PG490-88-treated groups compared to the bleomycin-treated group. Additionally, triptolide blocked bleomycin-induced increase in TGF-β mRNA in cultured normal human lung fibroblasts. The efficacy of PG490-88 when administered late after bleomycin installation suggests a potential role in the treatment of idiopathic pulmonary fibrosis. |
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ISSN: | 0002-9440 1525-2191 |
DOI: | 10.1016/S0002-9440(10)64046-1 |