Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Staphylococcal Enterotoxin A-Induced Toxic Shock

Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Staphylococcal Enterotoxin A-Induced Toxic Shock
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DOI:
10.1128/iai.00730-15
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发表时间:
2015-09-01
影响因子:
3.1
通讯作者:
Nakane, Akio
Nakane, Akio
中科院分区:
医学2区
文献类型:
--
作者:
Asano, Krisana;Yoshimura, Sayuri;Nakane, Akio

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脂肪组织源性干细胞(ASC)是从脂肪组织中分离出来的间充质基质细胞,具有免疫调节作用,具有多种应用前景,包括炎症性疾病的治疗。在本研究中,研究了 ASC 对细菌毒素诱导的炎症的影响。腹腔注射 ASC 可将小鼠从由脂多糖增强的葡萄球菌肠毒素 A (SEA) 诱导的致死性休克中拯救出来。在施用 ASC 的小鼠的血清和/或脾脏中,促炎细胞因子的产生减少,包括干扰素 γ、肿瘤坏死因子 α、白细胞介素 6 (IL-6) 和 IL-2。通过定量实时 PCR,施用 ASC 的小鼠中 Foxp3 的表达没有改变。另一方面,IL-12受体和STAT4的表达随着ASC施用而降低。这些结果意味着 ASC 的作用不涉及调节性 T 细胞的谱系,但这些细胞可能调节 T(H)1 分化。这一信息提供的证据表明,ASC 具有有效减轻 SEA 引起的中毒性休克的特性,并应促进对细菌毒素或细菌感染引起的其他炎症性疾病的进一步探索。
Adipose tissue-derived stem cells (ASCs), which are mesenchymal stromal cells isolated from adipose tissues, exhibit immunomodulatory effects that are promising for several applications, including the therapeutics of inflammatory diseases. In the present study, the effect of ASCs on bacterial toxin-induced inflammation was investigated. Intraperitoneal administration of ASCs rescued mice from lethal shock induced by staphylococcal enterotoxin A (SEA) potentiated with lipopolysaccharide. In the sera and/or spleens of mice administered ASCs, the production of proinflammatory cytokines, including interferon gamma, tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-2 was reduced. By quantitative real-time PCR, the expression of Foxp3 in the mice administered ASCs was not altered. On the other hand, the expression of IL-12 receptor and STAT4 was decreased with ASC administration. These results imply that the effect of ASCs is not involved in the lineage of regulatory T cells but that these cells may modulate T(H)1 differentiation. This information provides evidence that ASCs have properties that are effective to attenuate SEA-induced toxic shock and should prompt further exploration on other inflammatory diseases caused by bacterial toxins or bacterial infections.