姜黄素对脂多糖联合干扰素γ诱导的巨噬细胞炎症因子表达的影响及其机制

Effect of Curcumin on the Expression of Inflammatory Cytokines in Macrophages Induced by LPS Combined with IFN-γ and Its Mechanism

目的探讨姜黄素对脂多糖联合干扰素γ诱导的巨噬细胞表达炎症因子的影响及其相关机制。方法用脂多糖联合干扰素γ诱导巨噬细胞构建炎症细胞模型并设立不同浓度的姜黄素干预组和对照组,通过实时荧光定量PCR及酶联免疫吸附法测定不同分组中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)及白细胞介素12B(IL-12B)三种炎症因子的表达。Western blot检测各组细胞TLR4-MAPK/NF-κB信号通路的表达。结果实时荧光定量PCR显示,与对照组相比,姜黄素对脂多糖联合干扰素γ诱导的巨噬细胞TNF-α、IL-6及IL-12B m RNA的表达均具有明显抑制作用(P<0.001),酶联免疫吸附法也证实姜黄素能抑制以上炎症因子的分泌(P<0.01)。Western blot检测显示,姜黄素能明显抑制TLR4的表达及下游MAPK(p38、ERK1/2及JNK1/2)和NF-κB(IκBα及p65)通路的磷酸化(P<0.05)。结论姜黄素可通过抑制TLR4-MAPK/NF-κB信号通路抑制脂多糖联合干扰素γ诱导的巨噬细胞中TNF-α、IL-6及IL-12B这三种炎症因子的表达。

Ahn To investigate the effects of curcumin on the inflammatory cytokines in macrophages induced by LPS combined with IFN-γ and its molecular mechanism. Methods THP-1 cells were differentiated to macrophages before induced by LPS combined with IFN-γ, then treated by different doses of cureumin （0 μmol/L, 7.5 μmol/L, 15 μmol/L and 30 μmol/L）, separately. The expression of TNF-α, IL-6 and IL-12B of each group were detected by real- time PCR and ELISA assay. Results Compared with the control group, the cytokine protein and mRNA expression of TNF-α, IL-6 and IL-12B were suppressed by curcumin in macrophages induced by LPS combined with IFN-γ （P 〈 0. 01 ）. Furthermore, curcumin significantly inhibited the expression of TLR4 and phosphorylation of ERK, JNK, p38 and NF-KB. Conclusions Curcumin can remarkably suppress synthesis of TNF-α, IL-6 and IL-12B in macrophages induced by LPS combined with IFN-γ through TLR4-MAPK/NF-κB pathway.