HMGB1 modulates inflammatory responses in LPS-activated macrophages
HMGB1 modulates inflammatory responses in LPS-activated macrophages
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DOI：
10.1007/s00011-006-6112-0
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发表时间：
2007-04-01
影响因子：
6.7
通讯作者：
El Gazzar, M.
中科院分区：
文献类型：
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作者：
El Gazzar, M.
目的：高迁移率族蛋白B1（HMGB 1）作为炎症的晚期介质，通过诱导和延长促炎细胞因子的产生，增强组织损伤和感染时的炎症反应。目的是调查是否HMGB 1介导这种影响，通过影响生产的抗炎mediators.Materials和方法：小鼠巨噬细胞RAW 264.7细胞用0.5 μ g/ml的LPS刺激和HMGB 1，TNF α，IL-1 β，IL-10和TGF-β 1在培养上清液中的水平，通过ELISA测定。结果：LPS刺激后8h HMGB I开始释放，48 h达高峰，48 h后HMGB I开始释放，48 h后HMGB I开始释放。8 h后观察到TNF α、IL-1 β、IL-10和TGF-β 1的显著（p < 0.05）产生。然而，虽然TNF α和IL-β的水平仍然升高，IL-10和TGF-β 1的释放显着下降刺激后24小时。当细胞在来自24小时LPS刺激培养物的条件培养基存在下刺激时，TNF α和IL-1 β的产生增加，而IL-10和TGF-β 1的释放和mRNA转录物减少。加入到条件培养基中的中和抗HMGB 1抗体reveresed these responses.Conclusions：HMGB 1通过诱导促炎症反应调节活化巨噬细胞中的炎症级联反应，同时抑制抗炎反应。
Objective: As a late mediator of inflammation, high mobility group box 1 protein (HMGB1) amplifies the inflammatory responses to tissue injury and infection by inducing and extending the production of proinflammaory cytokines. The aim was to investigate whether HMGB1 mediates such effects by affecting the production of anti-inflammatory mediators.Materials and methods: The murine macrophage RAW 264.7 cells were stimulated with 0.5 mu g/ml of LPS and the levels of HMGB1, TNF alpha, IL-1 beta, IL-10 and TGF-beta 1 in the culture supernatants were measured by ELISA. Also, the mRNA expression for IL-10 and TGF-beta 1 was assessed by RT-PCR.Results: LPS induced HMGB I release at 8 h and reached a peak at 48 h. Significant (p < 0.05) production of TNF alpha, IL-1 beta, IL-10, and TGF-beta 1 was seen after 8 h. However, while the levels of TNF alpha and IL-beta remained elevated, IL-10 and TGF-beta 1 release markedly declined by 24 h after stimulation. When cells were stimulated in the presence of conditioned medium derived from a 24 h LPS-stimulated culture, the production of TNF alpha and IL-1 beta was increased while IL-10 and TGF-beta 1 release and mRNA transcripts were decreased. A neutralizing anti-HMGB1 antibody added to the conditioned media reveresed these responses.Conclusions: HMGB1 modulates the inflammatory cascade in activated macrophages by inducing proinflammatory, while suppressing anti-inflammatory responses.