Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cells in Vitro
Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cells in Vitro
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DOI：
10.1159/000354446
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发表时间：
2013-08
影响因子：
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通讯作者：
Yabo Mei;Wei-qin Zhou;Xiao-ying Zhang;Xiujuan Wei;Zhi-Chun Feng
中科院分区：
文献类型：
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作者：
Yabo Mei;Wei-qin Zhou;Xiao-ying Zhang;Xiujuan Wei;Zhi-Chun Feng
背景资料：虽然最近已经报道了不同类型的人间充质干细胞（hMSCs）上的Toll样受体（TLR）的表达，但是关于TLR 4的存在以及其对人沃顿氏骨髓源性MSC（hWJ-MSCs）的参与和影响仍然存在争议。方法：采用脂多糖（lipopolysaccharide，LPS）刺激hWJ-MSCs，观察TLR 4在hWJ-MSCs中的表达及作用。分析LPS致敏的hWJ-MSCs的增殖、凋亡和旁分泌因子的表达。结果：TLR 4在RNA水平上有高表达，但在蛋白水平上表达很低。hWJ-MSCs对LPS刺激有应答，并开始显著上调炎性细胞因子（IL-1α、IL-1β、IL-6和IL-8）的产生。LPS刺激hWJ-MSCs后，吲哚胺2，3-双加氧酶（IDO）-1、Cox 2、干扰素（IFN）-β和基质金属蛋白酶（MMP）-2表达上调，MMP-9表达下调，影响hWJ-MSCs的免疫抑制能力。结论：这些数据表明，LPS参与塑造hWJ-MSCs，并导致促炎细胞因子和抑制性免疫介质的产生，表明TLR 4激动剂诱导hWJ-MSCs极化至促炎和免疫抑制状态，这可能有利于探索hWJ-MSCs的临床潜力。
Background: Although the expression of toll-like receptors (TLRs) on different types of human mesenchymal stem cells (hMSCs) has recently been reported, controversy remains regarding the presence of TLR4 as well as its engagement and impact on human Wharton's jelly-derived MSCs (hWJ-MSCs). Methods: In the present study, the expression and role of TLR4 in hWJ-MSCs was investigated using a model of lipopolysaccharide (LPS). Proliferation, apoptosis, and the expression of paracrine factors in hWJ-MSCs primed with LPS were analysed. Results: The expression of TLR4 was high at the RNA level but very low at the protein level. hWJ-MSCs responded to LPS stimulation and initiated a marked up-regulation of inflammatory cytokine (IL-1α, IL-1β, IL-6, and IL-8) production. Moreover, hWJ-MSCs LPS stimulation resulted in the up-regulation of indoleamine 2,3-dioxygenase [IDO]-1, Cox2, interferon [IFN]-β, and matrix metalloproteinase (MMP)-2 but a down-regulation of MMP-9, which affect the immunosuppressive potential of hWJ-MSCs. Conclusions: These data suggest that LPS engagement shapes hWJ-MSCs and results in the production of pro-inflammatory cytokines and inhibitory immune mediators, showing TLR4 agonist induces the hWJ-MSCs polarization to a pro-inflammatory and immunosuppressive state, which may be beneficial for the exploration of the clinical potential of hWJ-MSCs.