Abstract
Triptolide (PG490, 97% pure) is a diterpenoid triepoxide with potent anti-inflammatory and immunosuppressive effects in transformed human bronchial epithelial cells and T cells (Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC-H, and Kao PN. J Biol Chem 274: 13443-13450, 1999). Triptolide, with an IC50 of ~20-50 ng/ml, inhibits normal and transformed human bronchial epithelial cell expression of interleukin (IL)-6 and IL-8 stimulated by phorbol 12-myristate 13-acetate (PMA), tumor necrosis factor-α, or IL-1β. Nuclear runoff and luciferase reporter gene assays demonstrate that triptolide inhibits IL-8 transcription. Triptolide also inhibits the transcriptional activation, but not the DNA binding, of nuclear factor-κB. A cDNA array and clustering algorithm analysis reveals that triptolide inhibits expression of the PMA-induced genes tumor necrosis factor-α, IL-8, macrophage inflammatory protein-2α, intercellular adhesion molecule-1, integrin β6, vascular endothelial growth factor, granulocytemacrophage colony-stimulating factor, GATA-3, fra-1, and NF45. Triptolide also inhibits constitutively expressed cell cycle regulators and survival genes cyclins D1, B1, and A1, cdc-25, bcl-x, and c-jun. Thus anti-inflammatory, antiproliferative, and proapoptotic properties of triptolide are associated with inhibition of nuclear factor-κB signaling and inhibition of genes known to regulate cell cycle progression and survival.
Original language | English (US) |
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Pages (from-to) | L958-L966 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 279 |
Issue number | 5 23-5 |
DOIs | |
State | Published - 2000 |
Keywords
- Atlas cDNA array
- Cyclin
- Interleukin-8
- Nuclear factor-κB
- Transcription
- Tripterygium
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology