Imaizumi Tadaatsu, Kumagai Mika, Hatakeyama Masaharu, Tamo Wakako, Yamashita Koji, Tanji Kunikazu, Yoshida Hidemi, Satoh Kei
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-4562, Japan.
Prostaglandins Other Lipid Mediat. 2003 Jul;71(3-4):293-9. doi: 10.1016/s1098-8823(03)00051-0.
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-delta 12,14-prostaglandin J2 (15d-PGJ2) is a ligand for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and modulates inflammatory reactions by regulating the expression of various genes. We studied the effect of 15d-PGJ2 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-PGJ2 inhibited the LPS-induced GM-CSF expression in a concentration-dependent manner; but ciglitazone, another agonist for PPAR-gamma, had no effect. This suggests that 15d-PGJ2 inhibits GM-CSF expression through a mechanism unrelated to PPAR-gamma. 15d-PGJ2 induced, by itself, the expression of interleukin-8, a potent proinflammatory chemokine, in HUVEC. 15d-PGJ2 may regulate inflammatory reactions by controlling the balance of various cytokines.
粒细胞巨噬细胞集落刺激因子(GM-CSF)是主要的造血生长因子之一,可激活成熟白细胞。GM-CSF由脂多糖(LPS)刺激的内皮细胞产生,LPS诱导的GM-CSF产生可能在内皮表面中性粒细胞的激活中起重要作用。15-脱氧-δ12,14-前列腺素J2(15d-PGJ2)是过氧化物酶体增殖物激活受体γ(PPAR-γ)的配体,通过调节各种基因的表达来调节炎症反应。我们研究了15d-PGJ2对内皮细胞中LPS诱导的GM-CSF表达的影响。培养人脐静脉内皮细胞(HUVEC),分别通过逆转录-聚合酶链反应和酶联免疫吸附测定分析GM-CSF mRNA和蛋白的表达。15d-PGJ2以浓度依赖的方式抑制LPS诱导的GM-CSF表达;但另一种PPAR-γ激动剂吡格列酮没有作用。这表明15d-PGJ2通过与PPAR-γ无关的机制抑制GM-CSF表达。15d-PGJ2自身可诱导HUVEC中白细胞介素-8(一种强效促炎趋化因子)的表达。15d-PGJ2可能通过控制各种细胞因子的平衡来调节炎症反应。