Kim Hyo Y, Kim Hyun K, Kim Jae R, Kim Hee S
Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Korea.
Immunol Cell Biol. 2005 Jun;83(3):286-93. doi: 10.1111/j.1440-1711.2005.01329.x.
15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) was initially identified as a high affinity natural ligand for the peroxisome proliferator-activated receptor (PPAR)-gamma. Recent studies have shown that it has a potent anti-inflammatory effect by attenuating the expression of proinflammatory mediators in activated macrophages, mainly through the inhibition of nuclear factor (NF)-kappaB-dependent transcription of inflammatory genes. In this study, we investigated the synergistic effect of 15d-PGJ(2) on the expression of LPS-induced chemokine KC mRNA in mouse peritoneal macrophages. The time course of KC mRNA expression in cells stimulated with 15d-PGJ(2) plus LPS simultaneously (15d-PGJ(2)/LPS) showed similar patterns to the cells treated with LPS alone, and 15d-PGJ(2) had no effect on the stability of LPS-induced KC mRNA expression. Although NF-kappaB activity in cells treated with LPS was augmented by 15d-PGJ(2), pyrrolidone dithiocarbamate (PDTC) did not block the synergistic effect of 15d-PGJ(2) on LPS-induced KC mRNA expression. However, the synergistic effect of 15d-PGJ(2) was markedly inhibited when the macrophages were treated with a inhibitor of the mitogen-activated protein kinase (MAPK) signalling pathway, 2'-amino-3'-methoxyflavine (PD98059). Therefore, the mechanism of synergistic action of 15d-PGJ(2) on the expression of LPS-induced KC mRNA in mouse peritoneal macrophages is possibly related to the MAPK signalling pathway, not to NF-kappaB activation. These data may contribute to unravelling some of the different mechanisms contrary to the anti-inflammatory effect of 15d-PGJ(2).
15-脱氧-Δ(12,14)-前列腺素J2（15d-PGJ2）最初被鉴定为过氧化物酶体增殖物激活受体（PPAR）-γ的高亲和力天然配体。最近的研究表明，它通过减弱活化巨噬细胞中促炎介质的表达而具有强大的抗炎作用，主要是通过抑制核因子（NF）-κB依赖性炎症基因的转录。在本研究中，我们研究了15d-PGJ2对小鼠腹腔巨噬细胞中脂多糖（LPS）诱导的趋化因子KC mRNA表达的协同作用。同时用15d-PGJ2加LPS刺激的细胞（15d-PGJ2/LPS）中KC mRNA表达的时间进程与单独用LPS处理的细胞相似，并且15d-PGJ2对LPS诱导的KC mRNA表达的稳定性没有影响。尽管15d-PGJ2增强了用LPS处理的细胞中的NF-κB活性，但吡咯烷二硫代氨基甲酸盐（PDTC）并未阻断15d-PGJ2对LPS诱导的KC mRNA表达的协同作用。然而，当巨噬细胞用丝裂原活化蛋白激酶（MAPK）信号通路抑制剂2'-氨基-3'-甲氧基黄酮（PD98059）处理时，15d-PGJ2的协同作用被显著抑制。因此，15d-PGJ2对小鼠腹腔巨噬细胞中LPS诱导的KC mRNA表达的协同作用机制可能与MAPK信号通路有关，而与NF-κB激活无关。这些数据可能有助于揭示与15d-PGJ2抗炎作用相反的一些不同机制。
