Culture medium from TNF-α-stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms
Culture medium from TNF-α-stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms
复制标题
来自 TNF-α 刺激的间充质干细胞的培养基通过多种抗过敏机制减轻过敏性结膜炎
DOI：
10.1016/j.jaci.2014.12.1926
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发表时间：
2015-08-01
影响因子：
14.2
通讯作者：
Liang, Dan
中科院分区：
文献类型：
--
作者：
Su, Wenru;Wan, Qian;Liang, Dan
背景资料：间充质干细胞（mesenchymal stem cells，MSCs）的免疫调节和抗炎作用已在多种自身免疫性/炎症性疾病中得到证实，但其在过敏性结膜炎中的作用及其抗过敏机制尚不清楚。目的：探讨MSCs在实验性过敏性结膜炎（experimental allergic conjunctivitis，EAC）中的临床应用及其抗过敏机制。将来自TNF-α刺激的骨髓源性MSC（MSC-CMT）的培养基局部给予患有EAC的小鼠，并评价相关的过敏症状和生物学变化。体外培养小鼠脾源性B细胞、骨髓源性肥大细胞（MCs）和肺血管内皮细胞，研究MSC-CMT的抗过敏机制。结果：局部滴注MSC-CMT可显著减轻豚草花粉诱发的EAC的临床症状，并显著降低炎性细胞频率、核因子kB p65表达、TNF-α和IL-4的产生。在体外MSC-CMT显着抑制MC的激活和B细胞IgE的释放，并减少组胺诱导的血管通透性增高。在EAC期间，MSC-CMT治疗还降低了IgE产生、组胺释放、MC富集和活化以及结膜血管通透性过高。MSC-CMT介导的B细胞，MCs，组胺和EAC期间的抗过敏作用被废除时，骨髓间充质干细胞预处理与COX 2小干扰RNA.Conclusions：我们的研究结果提供了令人信服的证据，MSC-CMT抑制EAC通过COX 2依赖的多种抗过敏机制，并支持使用MSC-CMT作为一种新的策略治疗过敏性结膜炎。
Background: The immunomodulatory and anti-inflammatory functions of mesenchymal stem cells (MSCs) have been demonstrated in several autoimmune/inflammatory diseases, but their contribution to allergic conjunctivitis and underlying antiallergic mechanisms remain elusive.Objective: We sought to explore the clinical application of MSCs to experimental allergic conjunctivitis (EAC) and its underlying antiallergic mechanisms.Methods: Culture medium from TNF-alpha-stimulated, bone marrow-derived MSCs (MSC-CMT) was administered topically to mice with EAC, and the related allergic symptoms and biological changes were evaluated. Murine spleen-derived B cells, bone marrow-derived mast cells (MCs), and lung vascular endothelial cells were cultured in vitro to investigate the antiallergic MSC-CMT mechanisms.Results: Topical instillation of MSC-CMT significantly attenuated the clinical symptoms of short ragweed pollen-induced EAC, with a significant decrease in inflammatory cell frequency, nuclear factor kB p65 expression, and TNF-alpha and IL-4 production. In vitro MSC-CMT significantly inhibited the activation of MCs and B-cell IgE release and reduced histamine-induced vascular hyperpermeability. During EAC, MSC-CMT treatment also decreased IgE production, histamine release, enrichment and activation of MCs, and conjunctival vascular hyperpermeability. The MSC-CMT-mediated inhibition of B cells, MCs, and histamine and its antiallergic effects during EAC were abrogated when MSCs were pretreated with COX2 small interfering RNA.Conclusions: Our findings provide compelling evidence that MSC-CMT inhibits EAC through COX2-dependent multiple antiallergic mechanisms and support the use of MSC-CMT as a novel strategy for treating allergic conjunctivitis.