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

PPAR gamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPAR gamma -ligands, 15-deoxy-Delta (12,14) prostaglandin-J(2) (15d-PGJ(2)), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC-1). Expression of PPAR gamma in HMEC-1 was confirmed by RT-PCR. Both PPAR gamma -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-PGJ(2) 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-PGJ(2) is a potent inducer of IL-8 production and can be a mediator of inflammatory response, but this effect is independent of PPAR gamma activation. (C) 2001 Elsevier Science Inc. All rights reserved.