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通过诱导 IFN-γ,嗜热链球菌 ST28 抑制 Th17 反应。

Suppression of Th17 response by Streptococcus thermophilus ST28 through induction of IFN-γ.

机构信息

Graduate School of Biosphere Science, Hiroshima University, Higashi-Ηiroshima, Japan.

出版信息

Int J Mol Med. 2011 Nov;28(5):817-22. doi: 10.3892/ijmm.2011.755. Epub 2011 Jul 20.

DOI:10.3892/ijmm.2011.755
PMID:21887477
Abstract

The proinflammatory cytokine interleukin (IL)-17 plays important roles in various inflammatory diseases, and IL-17-producing T helper 17 cells (Th17) have received much attention. For therapy of Th17-mediated diseases, some reports have indicated the clinical efficacy of lactic acid bacteria, including Streptococcus thermophilus. In this study, we examined the mechanism for the suppressive effects of S. thermophilus ST28 on the Th17 response in murine splenocytes stimulated with transforming growth factor (TGF)-β plus IL-6. Stimulation with TGF-β plus IL-6 increased mRNA expression of IL-17 and its production in the splenocytes, but ST28 markedly suppressed both. Meanwhile, ST28 increased the mRNA expression of interferon (IFN)-γ as well as its production. Anti-IFN-γ completely cancelled the suppressive effect of ST28 on IL-17 production. From these data, it was concluded that IFN-γ induced by ST28 had an important role on the effect. A genomic DNA (10 µg/ml) from ST28 effectively suppressed IL-17 production, probably via the Toll-like receptor 9. Therefore, modulation of Th1/Th17 balance would be one of the mechanisms under which S. thermophilus ST28 exerts an anti-inflammatory effect.

摘要

促炎细胞因子白细胞介素 (IL)-17 在各种炎症性疾病中发挥重要作用,产生 IL-17 的辅助性 T 细胞 17 型(Th17)细胞受到了广泛关注。对于 Th17 介导的疾病的治疗,一些报道表明了包括嗜热链球菌(Streptococcus thermophilus)在内的一些乳酸菌具有临床疗效。在这项研究中,我们研究了嗜热链球菌 ST28 通过转化生长因子 (TGF)-β 加白细胞介素 (IL)-6 刺激的鼠脾细胞对 Th17 反应的抑制作用机制。TGF-β 加 IL-6 刺激增加了脾细胞中 IL-17 的 mRNA 表达及其产生,但 ST28 显著抑制了两者。同时,ST28 增加了干扰素 (IFN)-γ 的 mRNA 表达及其产生。抗 IFN-γ 完全取消了 ST28 对 IL-17 产生的抑制作用。根据这些数据,得出结论:ST28 诱导的 IFN-γ 在其作用中起重要作用。来自 ST28 的基因组 DNA(10μg/ml)有效地抑制了 IL-17 的产生,可能是通过 Toll 样受体 9 实现的。因此,调节 Th1/Th17 平衡可能是嗜热链球菌 ST28 发挥抗炎作用的机制之一。

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