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

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.