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鼠源骨髓来源巨噬细胞中罗伊氏乳杆菌 GG 通过激活 TLR2/MyD88/MAPK 信号通路促进 M1 极化。

Lactobacillus rhamnosus GG promotes M1 polarization in murine bone marrow-derived macrophages by activating TLR2/MyD88/MAPK signaling pathway.

机构信息

Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China) of the Ministry of Agriculture, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Animal Nutrition and Feed Sciences, College of Animal Sciences, Zhejiang University, Hangzhou, China.

National Animal Husbandry Service, Beijing, China.

出版信息

Anim Sci J. 2020 Jan-Dec;91(1):e13439. doi: 10.1111/asj.13439.

DOI:10.1111/asj.13439
PMID:32779289
Abstract

Lactobacillus rhamnosus GG (LGG) is increasingly applied in functional food products and acts as a probiotic model in nutritious and clinical studies. Increasing evidences have revealed the immune modulation of LGG on macrophages. The aim of this study is to investigate the effect of LGG on macrophage polarization of murine bone marrow-derived macrophages (BMDMs). BMDMs were treated with 10 colony-forming units (CFU)/ml LGG for 1.5, 3, and 6 hr. Results showed that LGG obviously upregulated the mRNA expression of M1-associated cytokines (p < .05), including interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS), whereas had no effect on the expression of M2-associated markers (p > .05), including arginase 1 (Arg1), mannose receptor, and chitinase-like protein 3 (YM1). Furthermore, LGG markedly increased the expression of pro-inflammatory cytokines (IL-12p40, cyclooxygenase-2 [COX-2], and interferon-γ [IFN-γ]) (p < .05) and anti-inflammatory cytokines (IL-10, IL-4, and transforming growth factor-β [TGF-β]) (p < .05). In addition, we also found that TLR2/MyD88/MAPK signaling pathway was required for LGG-induced M1 macrophage polarization and M1-related cytokines expression. Together, these findings demonstrate that probiotic LGG facilitates M1 polarization of BMDMs, suggesting that LGG may have an immunotherapeutic potential in regulating the host defense against pathogen invasion.

摘要

鼠李糖乳杆菌 GG(LGG)越来越多地应用于功能性食品产品中,并在营养和临床研究中作为益生菌模型。越来越多的证据表明 LGG 对巨噬细胞具有免疫调节作用。本研究旨在研究 LGG 对小鼠骨髓来源巨噬细胞(BMDM)极化的影响。BMDM 用 10 个集落形成单位(CFU)/ml 的 LGG 处理 1.5、3 和 6 小时。结果表明,LGG 明显上调 M1 相关细胞因子的 mRNA 表达(p<.05),包括白细胞介素 1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)和诱导型一氧化氮合酶(iNOS),而对 M2 相关标志物的表达无影响(p>.05),包括精氨酸酶 1(Arg1)、甘露糖受体和几丁质样蛋白 3(YM1)。此外,LGG 明显增加了促炎细胞因子(IL-12p40、环加氧酶-2(COX-2)和干扰素-γ(IFN-γ))(p<.05)和抗炎细胞因子(IL-10、IL-4 和转化生长因子-β(TGF-β))(p<.05)的表达。此外,我们还发现 TLR2/MyD88/MAPK 信号通路是 LGG 诱导 M1 巨噬细胞极化和 M1 相关细胞因子表达所必需的。总之,这些发现表明益生菌 LGG 促进了 BMDM 的 M1 极化,表明 LGG 可能在调节宿主防御病原体入侵方面具有免疫治疗潜力。

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