Life Science Research Center, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China.
Department of Spine, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
Clin Chim Acta. 2015 Feb 20;441:33-43. doi: 10.1016/j.cca.2014.12.007. Epub 2014 Dec 13.
Interferon-γ (IFN-γ), the sole member in type II IFN predominantly secreted by macrophages and T cells, is a critical regulator of immune function and provides a robust first line of defense against invading pathogens. Binding of IFN-γ to its receptor complex can activate a variety of downstream signaling pathways, particularly the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), to induce gene transcription within the target cells. This pro-inflammatory mediator is highly expressed in atherosclerotic lesions and promotes foam cell formation, but its effects on the atherogenesis are complex, with both pro- and anti-atherogenic properties. IFN-γ also contributes to the development of myocardial infarction and stroke, the two main atherosclerotic diseases. Inhibition of IFN-γ signaling may prevent the development of atherosclerosis and help treat atherosclerotic diseases. Since IFN-γ may also exert anti-atherogenic effects, the safety and efficacy of anti-IFN-γ treatment still require careful evaluation in the clinical setting. In the current review, we summarize recent progression on regulation and signaling pathways of IFN-γ, and highlight its roles in foam cell formation, atherosclerosis, myocardial infarction as well as stroke. An increased understanding of these processes will help to develop novel IFN-γ-centered therapies for atherosclerotic diseases.
干扰素-γ（IFN-γ）是唯一一种主要由巨噬细胞和 T 细胞分泌的 II 型 IFN，是免疫功能的关键调节剂，为抵御入侵病原体提供了强大的第一道防线。IFN-γ 与受体复合物的结合可以激活多种下游信号通路，特别是 Janus 激酶（JAK）/信号转导和转录激活因子（STAT），从而在靶细胞内诱导基因转录。这种促炎介质在动脉粥样硬化病变中高度表达，并促进泡沫细胞形成，但它对动脉粥样形成的影响是复杂的，具有促动脉粥样和抗动脉粥样形成的特性。IFN-γ 也有助于心肌梗死和中风这两种主要的动脉粥样硬化疾病的发展。抑制 IFN-γ 信号可能会阻止动脉粥样硬化的发展，并有助于治疗动脉粥样硬化疾病。由于 IFN-γ 也可能发挥抗动脉粥样作用，因此在临床环境中仍需要仔细评估抗 IFN-γ 治疗的安全性和疗效。在当前的综述中，我们总结了 IFN-γ 调节和信号通路的最新进展，并强调了它在泡沫细胞形成、动脉粥样硬化、心肌梗死和中风中的作用。对这些过程的深入了解将有助于开发以 IFN-γ 为中心的动脉粥样硬化疾病的新疗法。
