Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4H7, Canada.
Biology Department, Acadia University, Wolfville, NS B4P 2R6, Canada.
Front Biosci (Landmark Ed). 2022 Jan 24;27(2):43. doi: 10.31083/j.fbl2702043.
Inflammation is the body's response to injury or infection and is important for healing and eliminating pathogens; however, prolonged inflammation is damaging and may lead to the development of chronic inflammatory disorders. Recently, there has been interest in exploiting antimicrobial peptides (AMPs) that exhibit immunoregulatory activities to treat inflammatory diseases.
In this study, we investigated the immunomodulatory effects of lactoferrin-derived lactoferricin AMPs from three different species (bovine, mouse, and human) with subtle differences in their amino acid sequences that alter their antimicrobial action; to our knowledge, no other studies have compared their immunomodulatory effects. Macrophages, key players in the induction and propagation of inflammation, were used to investigate the effects of species-specific lactoferricin peptides on inflammatory processes.
Bovine lactoferricin was the only one of the three peptides studied that downregulated lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, in both human and mouse macrophages. Lactoferricin regulated inflammation through targeting LPS-activated nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Although the immunoregulatory role of lactoferricin during an inflammatory response is yet to be elucidated, further investigation with the use of animal models is warranted by the current findings.
The ability of lactoferricin, especially that of bovine origin, to downregulate macrophage-mediated inflammatory responses suggests potential for the development of this peptide as a novel immunotherapeutic agent in the treatment of chronic inflammatory conditions.
炎症是机体对损伤或感染的反应，对愈合和消除病原体很重要；然而，长期的炎症是有害的，可能导致慢性炎症性疾病的发展。最近，人们对利用具有免疫调节活性的抗菌肽（AMPs）来治疗炎症性疾病产生了兴趣。
在这项研究中，我们研究了三种不同物种（牛、鼠和人）来源的乳铁蛋白衍生的乳铁蛋白抗菌肽的免疫调节作用，它们的氨基酸序列略有不同，改变了它们的抗菌作用；据我们所知，没有其他研究比较过它们的免疫调节作用。巨噬细胞是诱导和传播炎症的关键细胞，我们用它来研究物种特异性乳铁蛋白抗菌肽对炎症过程的影响。
在所研究的三种肽中，只有牛乳铁蛋白抗菌肽能够下调脂多糖（LPS）诱导的人源和鼠源巨噬细胞中促炎细胞因子肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的表达。乳铁蛋白抗菌肽通过靶向 LPS 激活的核因子（NF）-κB 和丝裂原激活的蛋白激酶（MAPK）信号通路来调节炎症。尽管乳铁蛋白抗菌肽在炎症反应中的免疫调节作用尚待阐明，但鉴于目前的研究结果，进一步使用动物模型进行研究是有必要的。
乳铁蛋白抗菌肽，特别是牛源乳铁蛋白抗菌肽，能够下调巨噬细胞介导的炎症反应的能力表明，该肽有可能作为一种新型免疫治疗剂，用于治疗慢性炎症性疾病。
