Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a PPAR-gamma-independent manner

Prostaglandins Other Lipid Mediat. 2001 Oct;66(3):165-77. doi: 10.1016/s0090-6980(01)00155-1.


PPARgamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPARgamma-ligands, 15-deoxy-delta12,14 prostaglandin-J2 (15d-PGJ2), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC- 1). Expression of PPARgamma in HMEC-1 was confirmed by RT-PCR. Both PPARgamma-ligands tested induced the activation of PPAR, but the potency of ciglitazone was higher, as evidenced by luciferase assay. Resting HMEC-1 released about 150 pg/ml of IL-8 protein. Treatment with LPS increased the IL-8 secretion up to 1 ng/ml. 15d-PGJ2 potently and dose-dependently increased both the steady-state and LPS-induced generation of IL-8 mRNA and IL-8 protein. In contrast, neither basal nor LPS-elicited expression of IL-8 was influenced by ciglitazone. We conclude, that 15d-PGJ2 is a potent inducer of IL-8 production and can be a mediator of inflammatory response, but this effect is independent of PPARgamma activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival
  • Electrophoretic Mobility Shift Assay
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Humans
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Ligands
  • NF-kappa B / metabolism
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / metabolism*
  • Transfection
  • Up-Regulation / drug effects


  • Interleukin-8
  • Ligands
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • 9-deoxy-delta-9-prostaglandin D2
  • Prostaglandin D2
  • ciglitazone