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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。
Objective: To investigate the role of nuclear factor-κB (NF-κB) in upregulation of macrophages and foam cell inflammatory response in iron overload. Methods: Macrophages and foam cells were pretreated with NF-κB inhibitor, with or without added iron chelator deferoxamine (DFO) for 24 h. West-ern blot was used to detect the expression of extracellular matrix metalloproteinase Induction factor (EMMPRIN) protein expression. DFO stimulation was added to macrophages and foam cells, and the expression of NF-κB p65 protein in the nucleus was detected by Western blot. The macrophages and foam cells were pretreated with natural ligand of p38 MAPK signaling pathway inhibitor or retinaldehyde x receptor (RXR) and stimulated with DFO. The expression of NF-κB p65 protein in the nucleus was detected by Western blot. Results: NF-κB inhibitor could inhibit the up-regulation of EMMPRIN in macrophages and foam cells by DFO. DFO can promote the expression of NF-κB p65 protein in macrophages and foam cells. p38 MAPK pathway inhibitor or RXR ligand can inhibit DFO on the NF-κB p65 protein upregulation. Conclusion: NF-κB is involved in the process of EMMPRIN expression in macrophages and foam cells induced by low iron load. The inhibitory effect of RXR ligand on the up-regulation of inflammatory reaction induced by iron overload is related to the inhibition of NF-κB activation.