Hyaluronic acid fragments evoke Kupffer cells via TLR4 signaling pathway
Hyaluronic acid fragments evoke Kupffer cells via TLR4 signaling pathway
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透明质酸片段通过 TLR4 信号通路诱发 Kupffer 细胞
DOI：
10.1007/s11427-009-0002-y
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
王慧
中科院分区：
文献类型：
--
作者：
王慧
Kupffer细胞表达Toll样受体4(TLR4)，在肝脏缺血再灌注(I/R)损伤中发挥重要作用。透明质酸(HA)片段是高分子量HA(HMW-HA)的降解产物，在炎症条件下具有激活免疫细胞的能力。在这里，我们研究了HA片段是否可以激活Kupffer细胞，并分析了其潜在的机制。从野生型小鼠(WT、C3H/HEN)和TLR4突变小鼠(C3HEJ)分离Kupffer细胞，用酶消化和层析的方法制备HA片段。然后用HA片段或其他对照刺激刺激Kupffer细胞。Kupffer细胞的激活被估计为释放促炎细胞因子。检测Kupffer细胞p38MAPK通路的激活情况，并进行阻断实验。结果表明，HA片段在体外获得了激活Kupffer细胞的能力，这种能力依赖于TLR4，而不是由于脂多糖的污染。SB-203580对p38MAPK的抑制实验证实，p38MAPK参与了HA片段对枯否细胞的激活。这表明，HA片段是细胞外基质的主要糖胺多糖之一的降解产物，在TLR4信号通路介导的Kupffer细胞激活中发挥关键作用，该信号通路至少部分依赖于p38 MAPK的激活。
Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acquire the ability to activate immune cells under inflammatory conditions. Here we investigated whether HA fragments could activate Kupffer cells and analyzed the underlying mechanism. Kupffer cells were isolated from wild-type mice (WT, C3H/HeN) and TLR4 mutant mice (C3H/HeJ) and HA fragments were produced by the methods of enzyme digestion and chromatography. Then Kupffer cells were stimulated by HA fragments or other control stimuli. The activation of Kupffer cells was estimated as the release of pro-inflammatory cytokines. The activation of p38 MAPK pathway of Kupffer cells was checked and blocking experiments were done as well. The results indicated that HA fragments acquired the ability to activate Kupffer cellsin vitro, which was TLR4 dependent and not due to contamination of lipopolysaccharide. Experiments of p38 MAPK kinase inhibition by SB-203580 verified p38 MAPK was required in HA fragments induced Kupffer cells activation. This suggests that HA fragments, degradative products of one of the major glycosaminoglycans of the extracellular matrix, play critical roles in Kupffer cell activation mediated by TLR4 signaling pathway, which is, at least partially, dependent on p38 MAPK activation.
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影响因子：
6.1
作者：
Hui Wang;Zhuo Li;Heshui Wu;Yang Wang;Chun-fang Jiang;Qi-chang Zheng;Jinxiang Zhang
通讯作者：
Hui Wang;Zhuo Li;Heshui Wu;Yang Wang;Chun-fang Jiang;Qi-chang Zheng;Jinxiang Zhang
DOI：
10.1084/jem.20001858
发表时间：
2002-01-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Termeer C;Benedix F;Sleeman J;Fieber C;Voith U;Ahrens T;Miyake K;Freudenberg M;Galanos C;Simon JC
通讯作者：
Simon JC
影响因子：
4.4
作者：
Zhai, Y;Shen, XD;Kupiec-Weglinski, JW
通讯作者：
Kupiec-Weglinski, JW
DOI：
10.2174/187152806779010936
发表时间：
2006-12-01
期刊：
Inflammation & Allergy Drug Targets
影响因子：
--
作者：
Cantor, Jerome O.;Nadkarni, Priya P.
通讯作者：
Nadkarni, Priya P.
影响因子：
4.8
作者：
Vabulas, RM;Ahmad-Nejad, P;Wagner, H
通讯作者：
Wagner, H