Mei Ya-Bo, Zhou Wei-Qin, Zhang Xiao-Ying, Wei Xiu-Juan, Feng Zhi-Chun
Department of Pediatrics, BaYi Children's Hospital of The General Military Hospital of Beijing PLA, The clinical medical college in the Beijing Military Region of second military medical university of PLA, Beijing.
Cell Physiol Biochem. 2013;32(2):390-401. doi: 10.1159/000354446. Epub 2013 Aug 26.
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).
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.
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.
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.
尽管最近有报道称不同类型的人间充质干细胞(hMSCs)上 toll 样受体(TLRs)的表达情况,但关于 TLR4 的存在及其对人脐带华通氏胶来源的间充质干细胞(hWJ-MSCs)的作用和影响仍存在争议。
在本研究中,使用脂多糖(LPS)模型研究了 TLR4 在 hWJ-MSCs 中的表达和作用。分析了用 LPS 预处理的 hWJ-MSCs 中的增殖、凋亡及旁分泌因子的表达。
TLR4 在 RNA 水平上表达较高,但在蛋白质水平上非常低。hWJ-MSCs 对 LPS 刺激有反应,并引发炎症细胞因子(IL-1α、IL-1β、IL-6 和 IL-8)产生的显著上调。此外,hWJ-MSCs 的 LPS 刺激导致吲哚胺 2,3-双加氧酶[IDO]-1、Cox2、干扰素[IFN]-β和基质金属蛋白酶(MMP)-2 的上调,但 MMP-9 的下调,这影响了 hWJ-MSCs 的免疫抑制潜力。
这些数据表明,LPS 的作用塑造了 hWJ-MSCs,并导致促炎细胞因子和抑制性免疫介质的产生,表明 TLR4 激动剂诱导 hWJ-MSCs 极化为促炎和免疫抑制状态,这可能有利于探索 hWJ-MSCs 的临床潜力。