Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways

Mol Immunol. 2007 Apr;44(10):2686-96. doi: 10.1016/j.molimm.2006.12.003. Epub 2007 Jan 16.


Inhibition of dendritic cell (DC) migration into tissues and secondary lymphoid organs is an efficient way to induce immunosuppression and tolerance. CCR7 and PGE(2) are critical for DC migration to secondary lymphoid organs where DC initiate immune response. Triptolide, an active component purified from the medicinal plant Tripterygium Wilfordii Hook F., is a potent immunosuppressive drug capable of prolonging allograft survival in organ transplantation by inhibiting T cell activation and proliferation. Considering the essential role in T cell tolerance of DC migration to secondary lymphoid organs, here we demonstrate that triptolide can significantly inhibit LPS-triggered upregulation of CCR7 expression and PGE(2) production by inhibiting cyclooxygenase-2 (COX-2) expression in DC, thus impairing DC migration towards CCR7 ligand CCL19/MIP-3betain vitro. Moreover, triptolide-treated DC display impaired migration into secondary lymphoid organs and in vivo administration of triptolide also inhibits DC migration. Further studies show that the triptolide-mediated inhibitory effects of LPS-induced activation of phosphatidylinositol-3 kinase (PI3-K)/Akt and nuclear NF-kappaB activation are involved in down-regulation of COX-2 and CCR7 expression resulting in impaired migration to secondary lymphoid organs of DC. Therefore, inhibition of DC migration through decreasing COX-2 and CCR7 expression via PI3-K/Akt and NF-kappaB signal pathways provides additional mechanistic explanation for triptolide's immunosuppressive effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Chemokine CCL19
  • Chemokines, CC / metabolism
  • Cyclooxygenase 2 / metabolism*
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dinoprostone / metabolism
  • Diterpenes / pharmacology*
  • Epoxy Compounds / pharmacology
  • Immunosuppressive Agents / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors
  • Phenanthrenes / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Receptors, CCR7
  • Receptors, Chemokine / antagonists & inhibitors*
  • Receptors, Chemokine / metabolism


  • Ccl19 protein, mouse
  • Ccr7 protein, mouse
  • Chemokine CCL19
  • Chemokines, CC
  • Cytokines
  • Diterpenes
  • Epoxy Compounds
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • NF-kappa B
  • Phenanthrenes
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, CCR7
  • Receptors, Chemokine
  • triptolide
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt
  • Dinoprostone