15-Deoxy-Δ 12,14-prostaglandin J 2 inhibits the expression of granulocyte-macrophage colony-stimulating factor in endothelial cells stimulated with lipopolysaccharide

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of major hematopoietic growth factors, activates mature leukocytes. GM-CSF is produced by endothelial cells stimulated with lipopolysaccharide (LPS), and the LPS-induced GM-CSF production may play an important role in the activation of neutrophils on the endothelial surface. 15-Deoxy-Δ 12,14-prostaglandin J 2 (15d-PGJ 2) is a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ) and modulates inflammatory reactions by regulating the expression of various genes. We studied the effect of 15d-PGJ 2 on the LPS-induced GM-CSF expression in endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured and the expressions of GM-CSF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. 15d-PGJ 2 inhibited the LPS-induced GM-CSF expression in a concentration-dependent manner; but ciglitazone, another agonist for PPAR-γ, had no effect. This suggests that 15d-PGJ 2 inhibits GM-CSF expression through a mechanism unrelated to PPAR-γ. 15d-PGJ 2 induced, by itself, the expression of interleukin-8, a potent proinflammatory chemokine, in HUVEC. 15d-PGJ 2 may regulate inflammatory reactions by controlling the balance of various cytokines.