The role of metabolism in macrophage in Kidney diseases
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摘要: 巨噬细胞是人体免疫系统的重要组成,其广泛参与全身炎症反应和组织损伤修复等多个病理生理过程。肾脏巨噬细胞从肾脏发育初期即发挥着重要的作用,并持续参与到之后的炎症浸润,组织损伤、修复及纤维化等过程,影响了肾脏应对缺血、炎症等打击的远期预后。组织中的巨噬细胞在特定的微环境中可以分化为2个独立的表型,分别是经典活化巨噬细胞(M1)和替代活化巨噬细胞(M2)。M1型巨噬细胞由T辅助淋巴细胞(Th1)、γ干扰素(interferon-γ,IFN-γ)、细菌和真菌壁成分如脂多糖(lipopolysaccharide,LPS)等诱导产生,并通过释放多种细胞因子,促进炎症反应。巨噬细胞在白细胞介素4(interleukin 4,IL-4)、白细胞介素10(interleukin 10,IL-10)和转化生长因子β(TGF-β1)等作用下,转化为M2型,并发挥抗炎作用。前期已有研究显示巨噬细胞的表型及功能与其能量代谢模式息息相关,且巨噬细胞能量代谢模式的变化会进一步影响到其生物学功能,从而影响肾脏一系列病理生理变化的进程。因此,研究肾脏巨噬细胞不同表型及不同能量代谢模式下发挥生理作用的机制,有助于进一步明确肾脏在炎症及损伤等病理状态下的转归,从而为将来进一步发展免疫治疗起指导作用。Abstract: Macrophages are an important component of the human immune system, and they are widely involved in multiple pathophysiological processes such as systemic inflammatory response and tissue damage repair. Kidney macrophages play an important role since the early stages of kidney development, and continue to participate in subsequent inflammatory infiltration, tissue damage, repair and fibrosis, affecting the long-term prognosis after kidney injury. Macrophages can be broadly classified into two different subtypes, depending on their local microenvironment, classically activated(M1) and alternatively activated(M2) macrophages. M1 macrophages are produced by exposured to interferon(IFN)-γ or lipopolysaccharide(LPS) and are considered pro-inflammatory due to their capacity to release certain cytokines. IL-4, IL-10 and TGF-β1 can induce macrophages to M2 polarization, which have anti-inflammatory functions. There have been many studies show that the phenotype and function of macrophages are closely related to their metabolism patterns, and the changes in their metabolism patterns will further affect their biological function, then lead to series of changes in process of pathophysiological in the kidney. Therefore, studying the different phenotypes of kidney macrophages and the mechanisms of their physiological effects under different metabolism patterns will help to further clarify the kidney outcomes in pathological conditions, and guiding the further development of immunotherapy in the future.
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Key words:
- Kidney disease /
- Macrophage polarization /
- Metabolism
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