NF-κB在铁负荷过低上调炎症因子中的作用

Effect of nuclear factor(NF)-κB on induction of EMMPRIN by excessive low iron load in macrophages and foam cells

目的:探讨核转录因子(NF)-κB在铁负荷过低上调巨噬细胞、泡沫细胞炎症因子反应中的作用。方法:将巨噬细胞和泡沫细胞给予NF-κB抑制剂预处理,加入或不加入铁离子鳌合剂去铁胺(DFO)继续培养24 h,用West-ern blot测定细胞中细胞外基质金属蛋白酶诱导因子(EMMPRIN)蛋白的表达。于巨噬细胞和泡沫细胞中加入DFO刺激,用Western blot测定细胞核中NF-κB p65蛋白的表达。将巨噬细胞和泡沫细胞给予p38 MAPK信号通路抑制剂或视黄醛x受体(RXR)的天然配体预处理,加入DFO刺激,用Western blot测定细胞核中NF-κB p65蛋白的表达。结果:NF-κB抑制剂可抑制DFO对巨噬细胞、泡沫细胞中EMMPRIN上调的作用。DFO可促进巨噬细胞、泡沫细胞细胞核中NF-κB p65蛋白的表达。p38 MAPK通路抑制剂或RXR配体可抑制DFO对NF-κB p65蛋白水平上调的作用。结论:NF-κB参与了铁负荷过低上调巨噬细胞和泡沫细胞中EMMPRIN表达的过程。RXR配体对铁负荷过低上调炎症反应的抑制作用,同其抑制NF-κB激活有关。

AIM： To investigate the effect of NF-κB on the induction of EMMPRIN by excessive low iron load in macrophages and foam cells.METHODS： Thp-1 derived macrophages and foam cells were pre-treated with NF-κB inhibitor and then were stimulated with/without desferrioxamine（DFO） for 24 h.EMMPRIN expression was assayed by Western blot.Cells were stimulated with DFO for different time periods and nuclear NF-κB p65 protein levels were then assayed by Western blot.Cells were pre-treated with p38 MAPK inhibitors or RXR ligand and nuclear NF-κB p65 protein levels were assayed again by Western blot.RESULTS： NF-κB inhibitor blocked the induction of EMMPRIN by DFO stimulation,DFO enhanced nuclear NF-κB p65 protein levels in macrophages and foam cells and p38 MAPK inhibitor and RXR ligand significantly blocked DFO upregulation of NF-κB p65.CONCLUSION： NF-κB is involved not only in the excessive low iron load upregulation of EMMPRIN expression,but also in the RXR ligand downregulation of inflammatory factor in macrophages and foam cells.