TNFα and IL-1β influence the differentiation and migration of murine MSCs independently of the NF-κB pathway.
TNFα and IL-1β influence the differentiation and migration of murine MSCs independently of the NF-κB pathway.
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DOI：
10.1186/scrt492
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发表时间：
2014-08-27
影响因子：
7.5
通讯作者：
Murphy JM
中科院分区：
文献类型：
--
作者：
Sullivan CB;Porter RM;Evans CH;Ritter T;Shaw G;Barry F;Murphy JM
间充质干细胞 (MSC) 具有修复和再生组织、炎症部位并逃避宿主免疫系统的能力。因此，它们代表了治疗自身免疫炎症性疾病的一种有吸引力的疗法。然而，炎症性关节炎的体内小鼠研究结果相互矛盾，这可能是由于所使用的间充质干细胞的遗传背景所致。众所周知，炎症环境可能会影响 MSC 的特性，而就人骨髓来源的 MSC 而言，这可能是由核因子-κ-B (NF-κB) 通路介导的。我们试图确定促炎细胞因子是否改变了来自不同小鼠品系的小鼠 MSC 的分化和迁移能力，以及这是否由 NF-κB 介导。 FVB 和 BALB/c MSC 的分化和迁移是在不同浓度的肿瘤坏死因子-α (TNFα) 和白细胞介素 (IL)-1β 存在的情况下进行的，并且 NF-κB 通路通过以下两种方式之一受到抑制：用表达 NF-κB 超级阻遏物的腺病毒载体转导 MSC，或者通过添加 将姜黄素添加到培养基中。 BALB/c 和 FVB MSC 在体外对促炎细胞因子的作用敏感。 TNFα 和 IL-1β 抑制 BALB/c 成骨和脂肪生成以及 FVB 成骨。两种细胞类型向含有胎牛血清的培养基的迁移通过任一细胞因子的预刺激而增强。在这两种细胞类型中，细胞因子的作用都不会因 NF-κB 通路的废除而逆转。这些数据表明，来自不同遗传背景的小鼠 MSC 可能会受到炎症环境的影响，但这种影响方式并非由 NF-κB 介导，而人类 MSC 的情况却并非如此。这不是由 NF-κB 介导的。这些发现很重要，应该会影响小鼠间充质干细胞体内试验的解释以及炎症性疾病临床前研究的未来发展。本文的在线版本 (doi:10.1186/scrt492) 包含补充材料，可供授权用户使用。
Mesenchymal stem cells (MSCs) have the ability to repair and regenerate tissue, home to sites of inflammation, and evade the host immune system. As such, they represent an attractive therapy for the treatment of autoimmune inflammatory diseases. However, results from in vivo murine studies in inflammatory arthritis have been conflicting, and this may be due to the genetic background of the MSCs used. It is known that the inflammatory milieu may influence properties of MSCs and that, in the case of human bone marrow-derived MSCs, this may be mediated by the nuclear factor-kappa-B (NF-κB) pathway. We sought to determine whether pro-inflammatory cytokines altered the differentiation and migration capacity of murine MSCs from different mouse strains and whether this was mediated by NF-κB. The differentiation and migration of FVB and BALB/c MSCs were carried out in the presence of varying concentrations of tumor necrosis factor-alpha (TNFα) and interleukin (IL)-1β, and the NF-κB pathway was inhibited in one of two ways: either by transduction of MSCs with an adenoviral vector expressing a super-repressor of NF-κB or by the addition of curcumin to culture media. Both BALB/c and FVB MSCs were sensitive to the effect of pro-inflammatory cytokines in vitro. TNFα and IL-1β suppressed BALB/c osteogenesis and adipogenesis and FVB osteogenesis. The migration of both cell types toward media containing fetal bovine serum was augmented by pre-stimulation with either cytokine. In neither cell type were the cytokine effects reversed by abrogation of the NF-κB pathway. These data show that murine MSCs from different genetic backgrounds may be influenced by an inflammatory milieu in a manner that is not mediated by NF-κB, as is the case for human MSCs. This is not mediated by NF-κB. These findings are important and should influence how in vivo trials of murine MSCs are interpreted and the future development of pre-clinical studies in inflammatory diseases. The online version of this article (doi:10.1186/scrt492) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Eljaafari, Assia;Tartelin, Marie-Laure;Miossec, Pierre
通讯作者：
Miossec, Pierre
影响因子：
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作者：
Gonzalez, Manuel A.;Gonzalez-Rey, Elena;Delgado, Mario
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影响因子：
5.4
作者：
Doncarli, A;Stasiuk, LM;AbehsiraAmar, O
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AbehsiraAmar, O
影响因子：
20.3
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通讯作者：
Pittenger, MF
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20.3
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Corcione, A;Benvenuto, F;Uccelli, A
通讯作者：
Uccelli, A