番茄红素对脂多糖诱导巨噬细胞炎症反应的作用及其分子机制

Effects of Lycopene on Lipopolysaccharide-induced Inflammatory Response in Macrophages and Its Possible Molecular Mechanism

【目的】探讨番茄红素对脂多糖(LPS)所诱导的RAW264.7巨噬细胞炎症因子生成的影响及其作用的分子机制。【方法】分别用1、5、10μmol/L的番茄红素孵育细胞1h,再用1μg/mLLPS处理细胞不同时间,分别用Griess法和ELISA法检测RAW264.7巨噬细胞培养基中NO及IL-6的含量,用Western-blot检测核因子-κB(NF-κB)p65、磷酸化和非磷酸化I-κBα、丝裂原活化蛋白激酶(MAPKs)的蛋白表达量。【结果】番茄红素能有效地降低炎性因子NO和IL-6分泌,进一步研究显示番茄红素能够抑制LPS诱导I-κBα磷酸化和降解、NF-κB核转移,阻断ERK1/2和p38MAPK激活,而对JNK活化没有影响。【结论】番茄红素能够通过抑制ERK1/2和p38MAPK信号通路的激活而抑制巨噬细胞NF-κB依赖的炎症因子NO和IL-6生成,这可能是番茄红素防治一些炎症相关性疾病的作用机制之一。

[Objective] To investigate the effects of lycopene on lipopolysaccharide（LPS）-induced proinflammatory cytokines production in RAW264.7 cells and its possible molecular mechanism.[Methods] RAW264.7 cells were pretreated with 1,5,and 10 μmol/L lycopene for 1 h and then treated with 1 μg/mL LPS for different time.The LPS-induced NO and IL-6 release in macrophages were assayed by the methods of Griess and ELISA,respectively.Western blotting was used to analyze nuclear factor-κB（NF-κB） P65,phosphorylated and non-phosphorylated I-κBα,mitogen activated protein kinases（MAPKs） protein expression.[Results] Lycopene inhibited LPS-induced production of nitric oxide（NO） and interleukin-6（IL-6）.Further study showed that lycopene also inhibited LPS-induced I-κBα phosphorylation,I-κBα degradation,and NF-κB translocation.Moreover,lycopene blocked the phosphorylation of ERK1/2 and p38 MAP kinase but not c-Jun NH2-terminal kinase.[Conclusion] Lycopene inhibits the inflammatory response of RAW 264.7 cells to LPS through inhibiting ERK/p38MAP kinase and the NF-κB pathway,.which is one of the mechanisms responsible for preventing inflammation-related diseases by lycopene.