Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea.
College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea.
Front Cell Infect Microbiol. 2018 Aug 21;8:287. doi: 10.3389/fcimb.2018.00287. eCollection 2018.
The cellular oncogene c-Fos (c-Fos) is a component of activator protein 1 (AP1), a master transcriptional regulator of cells. The suppression of c-Fos signaling by siRNA treatment resulted in significant induction of TLR4, which subsequently activates p38 and ERK1/2 mitogen-activated protein kinases (MAPKs) and enhances F-actin polymerization, leading to an increase in phagocytosis. During infection, c-Fos signaling is induced, which activates the downstream innate-immunity signaling cascade for bacterial clearance. The inhibition of c-Fos signaling led to increased production of interleukin 10 (IL-10), which partially suppressed lysosome-mediated killing, resulting in increased survival of inside macrophages. We present evidence of the regulatory role played by the c-Fos pathway in proliferation during infection; however, this was independent of the anti- effect of this pathway. Another finding is the essential contribution of c-Fos/TRAIL to infected-cell necrosis, which is a key event in bacterial dissemination. These data provide the mechanism via which c-Fos participates in host defense mechanisms against infection and in bacterial dissemination by macrophages.
细胞癌基因 c-Fos（c-Fos）是激活蛋白 1（AP1）的组成部分，是细胞的主要转录调节因子。siRNA 处理抑制 c-Fos 信号会导致 TLR4 的显著诱导，随后激活 p38 和 ERK1/2 丝裂原激活蛋白激酶（MAPK），并增强 F-肌动蛋白聚合，导致吞噬作用增加。在感染期间，c-Fos 信号被诱导，这激活了用于清除细菌的下游先天免疫信号级联反应。抑制 c-Fos 信号导致白细胞介素 10（IL-10）的产生增加，这部分抑制了溶酶体介导的杀伤作用，导致巨噬细胞内的存活增加。我们提出了 c-Fos 途径在感染过程中增殖中发挥调节作用的证据；然而，这与该途径的抗作用无关。另一个发现是 c-Fos/TRAIL 对感染细胞坏死的重要贡献，这是细菌传播的关键事件。这些数据提供了 c-Fos 参与宿主防御机制对抗感染和巨噬细胞中细菌传播的机制。
