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短链脂肪酸和载脂蛋白在嗜酸粒细胞相关性疾病中的调节作用。

Role of Short Chain Fatty Acids and Apolipoproteins in the Regulation of Eosinophilia-Associated Diseases.

机构信息

Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria.

出版信息

Int J Mol Sci. 2021 Apr 22;22(9):4377. doi: 10.3390/ijms22094377.

Abstract

Eosinophils are key components of our host defense and potent effectors in allergic and inflammatory diseases. Once recruited to the inflammatory site, eosinophils release their cytotoxic granule proteins as well as cytokines and lipid mediators, contributing to parasite clearance but also to exacerbation of inflammation and tissue damage. However, eosinophils have recently been shown to play an important homeostatic role in different tissues under steady state. Despite the tremendous progress in the treatment of eosinophilic disorders with the implementation of biologics, there is an unmet need for novel therapies that specifically target the cytotoxic effector functions of eosinophils without completely depleting this multifunctional immune cell type. Recent studies have uncovered several endogenous molecules that decrease eosinophil migration and activation. These include short chain fatty acids (SCFAs) such as butyrate, which are produced in large quantities in the gastrointestinal tract by commensal bacteria and enter the systemic circulation. In addition, high-density lipoprotein-associated anti-inflammatory apolipoproteins have recently been shown to attenuate eosinophil migration and activation. Here, we focus on the anti-pathogenic properties of SCFAs and apolipoproteins on eosinophil effector function and provide insights into the potential use of SCFAs and apolipoproteins (and their mimetics) as effective agents to combat eosinophilic inflammation.

摘要

嗜酸性粒细胞是宿主防御的关键组成部分,也是过敏和炎症性疾病中的有效效应物。一旦被招募到炎症部位,嗜酸性粒细胞就会释放其细胞毒性颗粒蛋白以及细胞因子和脂质介质,有助于清除寄生虫,但也会加剧炎症和组织损伤。然而,最近的研究表明,在稳态下,嗜酸性粒细胞在不同组织中发挥着重要的稳态作用。尽管通过实施生物制剂在治疗嗜酸性粒细胞疾病方面取得了巨大进展,但仍需要新型疗法,这些疗法可以特异性靶向嗜酸性粒细胞的细胞毒性效应功能,而不会完全耗尽这种多功能免疫细胞类型。最近的研究发现了几种可减少嗜酸性粒细胞迁移和激活的内源性分子。这些包括短链脂肪酸(SCFAs),例如丁酸,丁酸由肠道共生菌大量产生,并进入全身循环。此外,高密度脂蛋白相关抗炎载脂蛋白最近被证明可以减弱嗜酸性粒细胞的迁移和激活。在这里,我们重点关注 SCFAs 和载脂蛋白对嗜酸性粒细胞效应功能的抗病原特性,并深入探讨 SCFAs 和载脂蛋白(及其类似物)作为有效药物来对抗嗜酸性粒细胞炎症的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2696/8122716/80ee7502d62d/ijms-22-04377-g001.jpg

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