引用

toll样受体(Toll-like receptor, TLRs)通过检测病原体相关分子模式(PAMPs)来感知宿主感染，在免疫系统中发挥着重要作用。与人体相关的乙醇剂量可以抑制通过TLRs介导的病原体诱导的细胞因子反应。目前的研究旨在通过确定乙醇是否通过抑制转录因子激活或转录后效应来抑制TLR3和TLR4介导的TNF-分泌，从而研究这种作用的机制。在NF-B报告小鼠中，LPS在体内对NF-B的激活被乙醇抑制(仅LPS产生1700035,300个任意单位的光发射;LPS +乙醇产量为56,12016880,p=0.04)。环己酰亚胺对蛋白质合成的抑制表明，聚I:C-或lps诱导的分泌TNF-是从头合成的，而不是从细胞存储中释放出来。通过实时RT-PCR，我们发现乙醇对LPS和聚I:C诱导的TNF-基因转录有抑制作用。利用肿瘤坏死因子-转换酶(TACE)抑制剂，我们发现TACE引起的脱落是病原体攻毒后TNF-释放的先决条件。流式细胞术研究乙醇是否通过抑制TACE而减少TNF-的分泌。在LPS处理的细胞中，乙醇降低了TNF-细胞表面表达和分泌。 For example, 4.690.60% of untreated cells were positive for cell surface TNF-, LPS increased this to 25.180.85%, which was inhibited by ethanol (86.8 mM) to 14.290.39% and increased by a TACE inhibitor to 57.880.62%. In contrast, cells treated with poly I:C had decreased secretion of TNF- but not cell surface expression. There was some evidence for inhibition of TACE by ethanol in the case of LPS, but decreased TNF- gene expression seems to be the major mechanism of ethanol action in this system.