Hofer Thomas P J, Bitterle Ellen, Beck-Speier Ingrid, Maier Konrad L, Frankenberger Marion, Heyder Joachim, Ziegler-Heitbrock Löms
GSF National Research Center for Environment and Health, Insitute for Inhalation Biology, Neuherberg, Germany.
J Leukoc Biol. 2004 May;75(5):856-64. doi: 10.1189/jlb.0803387. Epub 2004 Feb 13.
Little is known about health effects of ultrafine particles (UFP) found in ambient air, but much of their action may be on cells of the lung, including cells of the monocyte/macrophage lineage. We have analyzed the effects of diesel exhaust particles (DEP; SRM1650a) on human monocytes in vitro. DEP, on their own, had little effect on cyclooxygenase (COX)-2 gene expression in the Mono Mac 6 cell line. However, when cells were preincubated with DEP for 1 h, then stimulation with the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) induced an up-to fourfold-higher production of COX-2 mRNA with an average twofold increase. This costimulatory effect of DEP led to enhanced production of COX-2 protein and to increased release of prostaglandin E(2) (PGE(2)). The effect was specific in that tumor necrosis factor gene expression was not enhanced by DEP costimulation. Furthermore, costimulation with the TLR2 ligand Pam3Cys also led to enhanced COX-2 mRNA. DEP and LPS showed similar effects on COX-2 mRNA in primary blood mononuclear cells, in highly purified CD14-positive monocytes, and in monocyte-derived macrophages. Our data suggest that UFP such as DEP may exert anti-inflammatory effects mediated by enhanced PGE(2) production.
人们对环境空气中发现的超细颗粒物（UFP）对健康的影响知之甚少，但其大部分作用可能作用于肺部细胞，包括单核细胞/巨噬细胞谱系的细胞。我们已经在体外分析了柴油废气颗粒（DEP；SRM1650a）对人单核细胞的影响。单独的DEP对Mono Mac 6细胞系中环氧合酶（COX）-2基因表达几乎没有影响。然而，当细胞与DEP预孵育1小时，然后用Toll样受体4（TLR4）配体脂多糖（LPS）刺激时，诱导产生的COX-2 mRNA增加高达四倍，平均增加两倍。DEP的这种共刺激作用导致COX-2蛋白产生增加以及前列腺素E（2）（PGE（2））释放增加。这种作用具有特异性，因为DEP共刺激不会增强肿瘤坏死因子基因表达。此外，用TLR2配体Pam3Cys共刺激也会导致COX-2 mRNA增加。DEP和LPS在原代血液单核细胞、高度纯化的CD14阳性单核细胞以及单核细胞衍生的巨噬细胞中对COX-2 mRNA表现出相似的作用。我们的数据表明，诸如DEP之类的UFP可能通过增强PGE（2）产生介导抗炎作用。
