Goral Joanna, Choudhry Mashkoor A, Kovacs Elizabeth J
Department of Cell Biology, Loyola University Medical Center, Maywood, IL 60153, USA.
J Leukoc Biol. 2004 Mar;75(3):553-9. doi: 10.1189/jlb.0703350. Epub 2003 Nov 21.
Acute ethanol consumption has been linked to an increase in infectious complications in trauma and burn patients. Ethanol modifies production of a variety of macrophage-derived immunoregulatory mediators. Lipopolysaccharide (LPS), a potent stimulator of inflammatory responses in macrophages, activates several intracellular signaling pathways, including mitogen-activated protein kinases (MAPK). In the current study, we investigated the effect of acute ethanol exposure on in vivo activation of p38 and extracellularly regulated kinases 1 and 2 (ERK1/2) MAPK in murine macrophages and the corresponding, LPS-stimulated interleukin (IL)-6 production. We demonstrated that a single dose of ethanol transiently down-regulated p38 and ERK1/2 activation levels (3-24 h after treatment) and impaired IL-6 synthesis. Ethanol-related reduction in IL-6 production was not further affected by the presence of inhibitors of p38 and ERK1/2 (SB 202190 and PD 98059, respectively). These results demonstrate that acute ethanol exposure can impair macrophage IL-6 production and indicate that this effect may result from ethanol-induced alterations in intracellular signaling through p38 and ERK1/2.
急性乙醇摄入与创伤和烧伤患者感染并发症的增加有关。乙醇会改变多种巨噬细胞衍生的免疫调节介质的产生。脂多糖（LPS）是巨噬细胞中炎症反应的有效刺激物，可激活多种细胞内信号通路，包括丝裂原活化蛋白激酶（MAPK）。在本研究中，我们调查了急性乙醇暴露对小鼠巨噬细胞中p38以及细胞外调节激酶1和2（ERK1/2）MAPK体内激活的影响，以及相应的LPS刺激的白细胞介素（IL）-6产生。我们证明，单剂量乙醇可短暂下调p38和ERK1/2的激活水平（治疗后3-24小时），并损害IL-6合成。p38和ERK1/2抑制剂（分别为SB 202190和PD 98059）的存在并未进一步影响乙醇相关的IL-6产生减少。这些结果表明，急性乙醇暴露可损害巨噬细胞IL-6的产生，并表明这种效应可能是由乙醇诱导的通过p38和ERK1/2的细胞内信号改变所致。
