Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang 110034, China.
Key Laboratory of Environment Pollution and Microecology of Liaoning Province, Shenyang 110034, China.
Mediators Inflamm. 2024 Feb 27;2024:8869510. doi: 10.1155/2024/8869510. eCollection 2024.
Inflammation is a complex host defensive response against various disease-associated pathogens. A baseline extent of inflammation is supposed to be tightly associated with a sequence of immune-modulated processes, resulting in the protection of the host organism against pathogen invasion; however, as a matter of fact is that an uncontrolled inflammatory cascade is the main factor responsible for the host damage, accordingly suggesting a significant and indispensable involvement of negative feedback mechanism in modulation of inflammation. Evidence accumulated so far has supported a repressive effect of the canonical Wnt/-catenin pathway on microbial-triggered inflammation via diverse mechanisms, although that consequence is dependent on the cellular context, types of stimuli, and cytokine environment. It is of particular interest and importance to comprehend the precise way in which the Wnt/-catenin pathway is activated, due to its essential anti-inflammatory properties. It is assumed that an inflammatory milieu is necessary for initiating and activating this signaling, implying that Wnt activity is responsible for shielding tissues from overwhelming inflammation, thus sustaining a balanced physiological condition against bacterial infection. This review gathers the recent efforts to elucidate the mechanistic details through how Wnt/-catenin signaling modulates anti-inflammatory responses in response to bacterial infection and its interactions with other inflammatory signals, which warrants further study for the development of specific interventions for the treatment of inflammatory diseases. Further clinical trials from different disease settings are required.
炎症是一种针对各种与疾病相关病原体的复杂宿主防御反应。基线程度的炎症应该与一系列免疫调节过程紧密相关,从而保护宿主免受病原体入侵;但事实上,不受控制的炎症级联反应是导致宿主损伤的主要因素,这表明负反馈机制在炎症调节中具有重要和不可或缺的作用。迄今为止的证据表明,经典的 Wnt/-连环蛋白途径通过多种机制对微生物触发的炎症具有抑制作用,尽管这种后果取决于细胞环境、刺激类型和细胞因子环境。由于其重要的抗炎特性,了解 Wnt/-连环蛋白途径被激活的确切方式具有特殊的意义和重要性。人们认为,炎症环境对于启动和激活这种信号至关重要,这意味着 Wnt 活性负责保护组织免受过度炎症的侵害,从而维持对抗细菌感染的平衡生理状态。这篇综述汇集了最近的努力,以阐明 Wnt/-连环蛋白信号如何通过调节对细菌感染的抗炎反应及其与其他炎症信号的相互作用来调节炎症反应的机制细节,这为开发针对炎症性疾病的特定干预措施的研究提供了依据。需要来自不同疾病环境的进一步临床试验。