细菌脂多糖及高迁移率族蛋白1对小鼠巨噬细胞M1/M2极化分型的影响

Effect of Lipopolysaccharide and HMGB1 on murine macrophage polarization

目的探讨细菌脂多糖(LPS)及信号转导通路中的下游分子高迁移率族蛋白1(HMGB1)对小鼠巨噬细胞M1/M2极化分型的作用。方法分别用LPS、HMGB1刺激小鼠巨噬细胞系RAW264.7,Q-PCR法检测各组巨噬细胞极化基因的表达情况。结果在LPS刺激下M1巨噬细胞极化基因NOS2、IL-6、TNF-α表达水平明显增高(P<0.01),M2巨噬细胞极化基因ARG-1、RELM-α表达水平降低(P>0.05),巨噬细胞往M1型分化。在HMGB1刺激下M1巨噬细胞极化基因NOS2、TNF-α和M2巨噬细胞极化基因RELM-α表达水平均明显增高(P<0.01)。结论 LPS使小鼠巨噬细胞往M1亚型分化促进炎症的发生发展;HMGB1作为LPS的一个下游分子,在使小鼠巨噬细胞往M1亚型分化的同时也能使其往M2方向分化,提示其中存在一个负反馈调节炎症的机制,避免机体组织受到无限制破坏。

Objective This study was performed to investigate the infection of Lipopolysaccharide（LPS）and its downstream cytokine High-mobility Group Box 1（HMGB1）on the transcriptional regulation of macrophagepolarization. Methods The murine macrophage cell line RAW246.7 was stimulated with LPS and HMGB1 respec-tively. The levels of M1 macrophage related m RNA（NOS2,TNF-α,IL-6）and M2 related m RNA（ARG-1,RELM-α）were determined by Q-PCR. Results The expression of M1 macrophage related m RNA（NOS2,IL-6,TNF-α）was significantly upregulated（P〈 0.01）,while the M2 macrophage related m RNA（ARG-1,RELM-α）was down-regulated（P〉0.05）after the stimulation of LPS. Both the M1 and M2 related markers were upregulated at them RNA level in HMGB1 stimulate group,and the upregulation of NOS2,TNF-α and RELM-α was statistically sig-nificant（P 〈0.01）. Conclusions LPS induces the M1 polarization of murine macrophage,which involved in theinflammation reaction. HMGB1,as the downstream cytokine of LPS signaling,induces both M1/M2 polarization ofmurine macrophage. It′ s inferred that HMGB1 intensifies periodontal inflammatory responses and,at the sametime,involves the negative feedback mechanism in the responses to tissue remodeling.