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Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages.
Innate Immunity ( IF 2.8 ) Pub Date : 2020-08-06 , DOI: 10.1177/1753425920942582
De Chang 1, 2 , Jingjing Feng 2 , Hongbo Liu 2 , Wei Liu 2 , Lokesh Sharma 2 , Charles S Dela Cruz 2
Affiliation  

Host response to lung infection includes coordinated efforts of multiple cell types, including the lung epithelium and macrophages. Importantly, both the lung epithelium and macrophages can internalize and clear invading pathogens. However, the mechanisms and their ability to internalize or phagocytose differ. Akt is a key cellular pathway that controls cell proliferation and survival, in addition to its role in host defense. The role of the Akt pathway was assessed using pharmacological Akt modulators in lung epithelial (A549) and macrophage (RAW 264.7) cell lines during Klebsiella bacterial infection. Our data show that the inhibition of the Akt pathway using specific Akt inhibitor MK2206 increased the phagocytic ability of lung epithelial cells but not of macrophages. In contrast, the activation of Akt using specific activator SC-79 decreased the phagocytic ability of epithelial cells, while it increased the phagocytic ability of macrophages. The altered phagocytic ability in both cell types using Akt modulators was not due to changes in bacterial adhesion to the host cell. The clinical usefulness of these Akt modulators may vary based on the type of infection and on the relative contribution of epithelial cells and macrophages in clearing the particular bacterial infection. The Akt pathway has differential roles in the internalization of Klebsiella bacteria by respiratory epithelial cells and immune cells.



中文翻译:

Akt 通路对肺上皮细胞和巨噬细胞对克雷伯氏菌内化的不同影响。

宿主对肺部感染的反应包括多种细胞类型的协同作用,包括肺上皮细胞和巨噬细胞。重要的是,肺上皮细胞和巨噬细胞都可以内化和清除入侵的病原体。然而,这些机制及其内化或吞噬能力是不同的。除了在宿主防御中发挥作用之外,Akt 是控制细胞增殖和存活的关键细胞通路。使用药理学 Akt 调节剂在克雷伯氏菌期间肺上皮 (A549) 和巨噬细胞 (RAW 264.7) 细胞系中评估 Akt 通路的作用细菌感染。我们的数据显示,使用特定的 Akt 抑制剂 MK2206 抑制 Akt 通路会增加肺上皮细胞的吞噬能力,​​但不会增加巨噬细胞的吞噬能力。相反,使用特异性激活剂 SC-79 激活 Akt 会降低上皮细胞的吞噬能力,​​而增加巨噬细胞的吞噬能力。使用 Akt 调节剂的两种细胞类型中吞噬能力的改变并不是由于细菌对宿主细胞的粘附发生了变化。这些 Akt 调节剂的临床用途可能因感染类型以及上皮细胞和巨噬细胞在清除特定细菌感染中的相对贡献而异。Akt 通路在克雷伯氏菌的内化中具有不同的作用 细菌通过呼吸道上皮细胞和免疫细胞。

更新日期:2020-08-08
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