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.
Jozkowicz
A
A
Department of Vascular Surgery, AKH, University of Vienna, Austria. alicia.jozkowicz@akh-wien.ac.at
Dulak
J
J
Prager
M
M
Nanobashvili
J
J
Nigisch
A
A
Winter
B
B
Weigel
G
G
Huk
I
I
D002460:Cell Line; D002470:Cell Survival; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D016209:Interleukin-8; D008024:Ligands; D016328:NF-kappa B; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2; C039671:ciglitazone