Effect of acrolein on human alveolar macrophage NF-kappaB activity.
Effect of acrolein on human alveolar macrophage NF-kappaB activity.
复制标题
丙烯醛对人肺泡巨噬细胞 NF-κB 活性的影响。
DOI：
10.1152/ajplung.1999.277.3.l550
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Holian,A
中科院分区：
文献类型：
--
作者：
Li,L;HamiltonJr,RF;Holian,A
丙烯醛是一种环境污染物，已知其抑制呼吸道宿主对感染的防御;然而，宿主防御降低的机制尚不清楚。我们以前曾报道，丙烯醛抑制内毒素诱导的细胞因子释放和诱导人肺泡巨噬细胞凋亡，这表明细胞因子释放的抑制和/或对肺泡巨噬细胞的细胞毒性可能是丙烯醛诱导的肺免疫抑制的部分原因。由于核因子-κB（NF-κB）是许多细胞因子基因的重要转录因子，也是细胞凋亡的重要调节因子，因此采用电泳迁移率变动法检测丙烯醛对NF-κB活性的影响。丙烯醛可剂量依赖性抑制内毒素诱导的NF-κB活化以及基础水平NF-κB活性。由于IκB是核中NF-κB活性的主要调节因子，因此通过Western印迹法测定IκB的变化。丙烯醛抑制IκB磷酸化导致细胞IκB水平增加，阻止NF-κB核转位，这可能是丙烯醛诱导的NF-κB活性抑制的机制。同时检测基础水平NF-κB在丙烯醛诱导的细胞凋亡中的作用。NF-κB抑制剂（MG-132）也可诱导人肺泡巨噬细胞凋亡，表明巨噬细胞存活可能需要一定的基础水平NF-κB活性。综上所述，我们的结果表明丙烯醛抑制内毒素诱导的NF-κB活化降低了基础水平的NF-κB活性，这可能是抑制细胞因子释放和诱导人肺泡巨噬细胞凋亡的原因。
Acrolein is an environmental pollutant that is known to suppress respiratory host defense against infections; however, the mechanism of the decrease in host defense is not yet clear. We have previously reported that acrolein inhibited endotoxin-induced cytokine release and induced apoptosis in human alveolar macrophages, suggesting that the inhibition of cytokine release and/or cytotoxicity to alveolar macrophages may, in part, be responsible for acrolein-induced immunosuppression in the lung. Because nuclear factor-κB (NF-κB) is an important transcription factor for a number of cytokine genes and is also an important regulator of apoptosis, the effect of acrolein on NF-κB activity was examined by electrophoresis mobility shift assay. Acrolein caused a dose-dependent inhibition of endotoxin-induced NF-κB activation as well as an inhibition of basal level NF-κB activity. Because IκB is a principal regulator of NF-κB activity in the nucleus, changes in IκB were determined by Western blotting. Acrolein-inhibited IκB phosphorylation leads to an increase in cellular IκB levels preventing NF-κB nuclear translocation and is likely the mechanism of acrolein-induced inhibition of NF-κB activity. The role of basal level NF-κB in acrolein-induced apoptosis was also examined. An NF-κB inhibitor (MG-132) also induced apoptosis in human alveolar macrophages, suggesting that a certain basal level NF-κB activity may be required for macrophage cell survival. Taken together, our results suggest that the acrolein-inhibited endotoxin-induced NF-κB activation decreased the basal level NF-κB activity, which may be responsible for the inhibition of cytokine release and the induction of apoptosis in human alveolar macrophages.