Kumagai Mika, Imaizumi Tadaatsu, Suzuki Katsuhiko, Yoshida Hidemi, Takanashi Shingo, Okumura Ken, Sugawarai Kazuo, Satoh Kei
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Tohoku J Exp Med. 2004 Feb;202(2):69-76. doi: 10.1620/tjem.202.69.
15-Deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) is an agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which plays an important role in various biological processes including inflammatory responses. We have addressed the effect of 15d-PGJ2 on the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a cell line derived from human bronchial epithelial cells (BEAS-2B). Besides being a hematopoietic growth factor, GM-CSF activates mature leukocytes and is involved in regulation of inflammatory responses. Cultures of BEAS-2B were stimulated with interleukin-1beta (IL-1beta), and the expressions of GM-CSF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. IL-1beta stimulated the expression of GM-CSF in BEAS-2B cells in concentration- and time-dependent manners. When the cells were pretreated with 15d-PGJ2 for 1 hour, the IL-1beta-induced GM-CSF expression was inhibited in a concentration-dependent manner (2-50 microM). Ciglitazone, another agonist of PPAR-gamma, did not affect the IL-1beta-induced GM-CSF expression in BEAS-2B cells. A PPAR-gamma antagonist, bisphenol A diglycide ether (BADGE), did not reverse the inhibitory effects of 15d-PGJ2 on GM-CSF expression. 15d-PGJ2 regulates GM-CSF expression in the bronchial epithelium, which may be mediated through a mechanism unrelated to PPAR-gamma.
15-脱氧-δ(12,14)-前列腺素J2（15d-PGJ2）是过氧化物酶体增殖物激活受体γ（PPAR-γ）的激动剂，PPAR-γ在包括炎症反应在内的各种生物学过程中发挥重要作用。我们研究了15d-PGJ2对源自人支气管上皮细胞（BEAS-2B）的细胞系中粒细胞-巨噬细胞集落刺激因子（GM-CSF）表达的影响。GM-CSF除了是一种造血生长因子外，还能激活成熟白细胞并参与炎症反应的调节。用白细胞介素-1β（IL-1β）刺激BEAS-2B细胞培养物，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。IL-1β以浓度和时间依赖性方式刺激BEAS-2B细胞中GM-CSF的表达。当细胞用15d-PGJ2预处理1小时时，IL-1β诱导的GM-CSF表达以浓度依赖性方式（2-50微摩尔）受到抑制。另一种PPAR-γ激动剂吡格列酮不影响BEAS-2B细胞中IL-1β诱导的GM-CSF表达。PPAR-γ拮抗剂双酚A二缩水甘油醚（BADGE）不能逆转15d-PGJ2对GM-CSF表达的抑制作用。15d-PGJ2调节支气管上皮中GM-CSF的表达，这可能通过与PPAR-γ无关的机制介导。
