Modulation of murine macrophage TLR7/8-mediated cytokine expression by mesenchymal stem cell-conditioned medium.
Modulation of murine macrophage TLR7/8-mediated cytokine expression by mesenchymal stem cell-conditioned medium.
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DOI：
10.1155/2013/264260
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发表时间：
2013
影响因子：
4.6
通讯作者：
Betsuyaku T
中科院分区：
文献类型：
--
作者：
Asami T;Ishii M;Fujii H;Namkoong H;Tasaka S;Matsushita K;Ishii K;Yagi K;Fujiwara H;Funatsu Y;Hasegawa N;Betsuyaku T
越来越多的证据表明间充质干细胞（MSC）在先天免疫反应中发挥抗炎作用。然而，人们对 MSC 或其分泌物对 Toll 样受体 (TLR) 7 和 TLR8（识别病毒单链 RNA (ssRNA) 的受体）的配体反应的影响知之甚少。巨噬细胞在针对 ssRNA 病毒感染的先天免疫反应中发挥着关键作用；因此，我们研究了 TLR7/8 配体刺激后 MSC 条件培养基对巨噬细胞细胞因子表达的影响。在用 TLR7/8 配体刺激后，与不使用 MSC 或在对照培养基中培养的巨噬细胞相比，使用 MSC 或在 MSC 条件培养基中培养的骨髓源性巨噬细胞分别表达较低水平的肿瘤坏死因子 (TNF) α 和白细胞介素 (IL) 6 以及较高水平的 IL-10。细胞因子表达的调节与 MSC 分泌的前列腺素 E2 (PGE2) 相关。 PGE2 增强细胞外信号相关激酶 (ERK) 信号传导并抑制核因子-κB (NF-κB) 信号传导。增强的 ERK 信号传导有助于增强 IL-10 的产生，而抑制 NF-κB 信号传导则导致 TNF-α 的产生减少。总的来说，这些结果表明 MSC 和 MSC 条件培养基在 TLR7/8 介导的刺激后调节巨噬细胞中的细胞因子表达谱，这表明 MSC 在 ssRNA 病毒感染期间发挥免疫调节作用。
Increasing evidence suggests that mesenchymal stem cells (MSCs) play anti-inflammatory roles during innate immune responses. However, little is known about the effect of MSCs or their secretions on the ligand response of Toll-like receptor (TLR) 7 and TLR8, receptors that recognize viral single-stranded RNA (ssRNA). Macrophages play a critical role in the innate immune response to ssRNA virus infection; therefore, we investigated the effect of MSC-conditioned medium on cytokine expression in macrophages following stimulation with TLR7/8 ligands. After stimulation with TLR7/8 ligand, bone marrow-derived macrophages cultured with MSCs or in MSC-conditioned medium expressed lower levels of tumor necrosis factor (TNF) α and interleukin (IL) 6 and higher levels of IL-10 compared to macrophages cultured without MSCs or in control medium, respectively. The modulations of cytokine expression were associated with prostaglandin E2 (PGE2) secreted by the MSCs. PGE2 enhanced extracellular signal-related kinase (ERK) signaling and suppressed nuclear factor-κB (NF-κB) signaling. Enhanced ERK signaling contributed to enhanced IL-10 production, and suppression of NF-κB signaling contributed to the low production of TNF-α. Collectively, these results indicate that MSCs and MSC-conditioned medium modulate the cytokine expression profile in macrophages following TLR7/8-mediated stimulation, which suggests that MSCs play an immunomodulatory role during ssRNA virus infection.
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影响因子：
3.8
作者：
Li, Xinyan;Jiang, Song;Tapping, Richard I.
通讯作者：
Tapping, Richard I.
DOI：
10.1152/ajplung.00253.2010
发表时间：
2011-09-01
影响因子：
4.9
作者：
Huh, Jin Won;Kim, Sun-Yong;Lee, Sang-Do
通讯作者：
Lee, Sang-Do
DOI：
10.1038/nri3166
发表时间：
2012-03-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.4
作者：
Gupta, Naveen;Su, Xiao;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
影响因子：
4.4
作者：
Keck, Simone;Freudenberg, Marina;Huber, Michael
通讯作者：
Huber, Michael