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(American Journal of Pathology. 2001;158:997-1004.)
© 2001 American Society for Investigative Pathology

Regular Articles

PG490-88, a Derivative of Triptolide, Blocks Bleomycin-Induced Lung Fibrosis

From the Division of Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, California

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)-ß in the bronchoalveolar lavage fluid showed a significant decrease in TGF-ß in the PG490-88-treated groups compared to the bleomycin-treated group. Additionally, triptolide blocked bleomycin-induced increase in TGF-ß 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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