Surfactin inhibits immunostimulatory function of macrophages through blocking NK-κB, MAPK and Akt pathway

Surfactin inhibits immunostimulatory function of macrophages through blocking NK-κB, MAPK and Akt pathway
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DOI:
10.1016/j.intimp.2009.03.013
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发表时间:
2009-07-01
影响因子:
5.6
通讯作者:
Kim, YoungHee
Kim, YoungHee
中科院分区:
医学2区
文献类型:
--
作者:
Park, Sun Young;Kim, YoungHee

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Surfactin 是最强大的生物表面活性剂之一,已知具有抗生素、抗肿瘤和抗炎功能。在这项研究中,我们研究了表面活性素对巨噬细胞抗原呈递特性的影响。测试了硫代乙醇酸盐引发的小鼠腹腔巨噬细胞的表面分子表达、细胞因子产生、吞噬作用、通过混合淋巴细胞反应诱导 T 细胞活化的能力以及潜在的信号传导途径。 Surfactin 显着抑制脂多糖诱导的 CD40、CD54、CD80 和 MHC-II 的表达,但不抑制 CD86 和 MHC-I 的表达。 Surfactin 处理的巨噬细胞还表现出吞噬功能受损和 IL-12 表达减少。 surfactin显着抑制CD4(+)T细胞的活化。暴露于表面活性素的巨噬细胞发现 NF-κ B p65 的易位和激活受损。此外,surfactin 抑制 I kappa B-alpha 的磷酸化和降解,并抑制 IKK、Akt、JNK 和 p38 激酶的激活。这些结果表明,surfactin 通过抑制 NF-kappa B、p38、JNK 和 Akt 来抑制 MHC-II 和共刺激分子的表达,从而损害巨噬细胞的抗原呈递功能。这些新发现为表面活性素在自身免疫性疾病和移植中的免疫药理学作用提供了新的见解。 (C) 2009 Elsevier B.V. 保留所有权利。
Surfactin is one of the most powerful biosurfactants, and is known to have antibiotic, anti-tumor and anti-inflammatory functions. In this study, we investigated the effect of surfactin on antigen-presenting property of macrophages. Thioglycollate-elicited mouse peritoneal macrophages were tested for surface molecule expression, cytokine production, phagocytosis, capacity to induce T cell activation by mixed lymphocyte reaction, and underlying signaling pathways. Surfactin significantly suppressed lipopolysaccharide-induced expression of CD40, CD54, CD80, and MHC-II, but not of CD86 and MHC-I. Surfactin-treated macrophages also exhibited impaired phagocytosis and reduced IL-12 expression. And surfactin markedly inhibited the activation of CD4(+) T cells. Impaired translocation and activation of NF-kappa B p65 were founded on macrophages exposed to surfactin. In addition, surfactin inhibited the phosphorylation and degradation of I kappa B-alpha, and suppressed the activation of IKK, Akt, JNK and p38 kinase. These results suggest that surfactin impair the antigen-presenting function of macrophages by inhibiting the expression of MHC-II and costimulatory, molecules via suppression of NF-kappa B, p38, JNK and Akt. These novel findings provide new insight into the immunopharmacological role of surfactin in autoimmune disease and transplantation. (C) 2009 Elsevier B.V. All rights reserved.