CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells.
CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells.
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DOI：
10.1038/srep23132
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发表时间：
2016-03-15
影响因子：
4.6
通讯作者：
Zang W
中科院分区：
文献类型：
--
作者：
Cao D;Luo J;Chen D;Xu H;Shi H;Jing X;Zang W
清道夫受体 CD36 参与病原体识别、吞噬作用和病原体诱导的信号传导。本研究探讨了 CD36 和 TLR4 在改变脂多糖 (LPS) 诱导的信号通路和介导原代山羊乳腺上皮细胞 (pGMEC) 中大肠杆菌 (E. coli) 内吞作用方面的关系。 CD36 表达的操作显着影响用 LPS 刺激 12 小时的 pGMEC 中 TLR4 和核因子 kappa B (NF-κB) mRNA 的表达。 NF-κB 和激活蛋白 1 (AP-1) 活性通过操纵 LPS 诱导的 pGMEC 中 CD36 的表达来调节。然而，CD36 介导的 AP-1 激活主要通过 c-Jun N 末端激酶 (c-JNK) 发生。衔接蛋白和促炎细胞因子也参与这些信号传导途径，并通过调节 LPS 刺激的细胞中的 CD36 表达来发挥作用。此外，在大肠杆菌模拟后，CD36 与 TLR4 协同参与 TLR4 介导的吞噬作用，但 LPS 处理不会诱导这种复合物。我们的研究首次阐明 CD36 作为反刍动物的清道夫受体。此外，这项研究表明，CD36 在 LPS 诱导的下游信号级联激活中发挥着至关重要的作用，并通过 pGMEC 中的 TLR4 介导大肠杆菌吞噬作用，这为乳腺炎提供了一种新的治疗策略。
The scavenger receptor CD36 is involved in pathogen recognition, phagocytosis, and pathogen-induced signaling. This study investigated the relationship between CD36 and TLR4 in modifying lipopolysaccharide (LPS)-induced signaling pathways and mediating Escherichia coli (E. coli) endocytosis in primary goat mammary epithelial cells (pGMECs). The manipulation of CD36 expression significantly influenced TLR4 and nuclear factor kappa B (NF-κB) mRNA expression in pGMECs stimulated with LPS for 12 h. NF-κB and activator protein-1 (AP-1) activity was regulated by the manipulation of CD36 expression in LPS-induced pGMECs. However, CD36-mediated AP-1 activation occurred primarily through c-Jun N-terminal kinase (c-JNK). Adaptor proteins and proinflammatory cytokines were also involved in these signaling pathways and acted by regulating CD36 expression in LPS-stimulated cells. Moreover, CD36 cooperated with TLR4 in TLR4-mediated phagocytosis following E. coli simulation, but this complex was not induced by LPS treatment. Our study is the first to illuminate CD36 as a scavenger receptor in ruminants. Additionally, this study indicates that CD36 plays a vital role in the LPS-induced activation of downstream signaling cascades and mediates E. coli phagocytosis via TLR4 in pGMECs, which offers a novel treatment strategy for mastitis.