Anti-inflammatory effects of triptolide in human bronchial epithelial cells

Guohua Zhao, Laszlo T. Vaszar, Daoming Qiu, Lingfang Shi, Peter N. Kao

Research output: Contribution to journalArticle

86 Scopus citations

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 languageEnglish (US)
Pages (from-to)L958-L966
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number5 23-5
DOIs
StatePublished - Jan 1 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

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