Jiang Rulan, Du Xiaogu, Lönnerdal Bo
Department of Nutrition, University of California, Davis.
J Pediatr Gastroenterol Nutr. 2014 Nov;59(5):642-52. doi: 10.1097/MPG.0000000000000481.
Lactoferrin (Lf) is an iron-binding glycoprotein present in high concentration in human milk. It is a pleiotropic protein and is involved in diverse bioactivities, such as stimulation of cell proliferation and differentiation, immune competence, antimicrobial activities, anti-infection, and anticancer activities. Lf has been shown to be partly resistant to proteolysis in the gastrointestinal tract and may thus play important roles in the intestine and liver during infancy. Talactoferrin alfa (TLf) is a recombinant human Lf shown to protect against sepsis and necrotizing enterocolitis as well as cancer. Because bovine Lf (bLf) and human Lf have different amino acid composition and all 3 Lfs differ in glycosylation, they may have different functions/potency. The objective of the present study was to investigate and compare bioactivities of TLf and Lfs from human and bovine milk and thus to provide a better understanding of the bioactivities of different forms of Lf and their potential applications.
In the present study, Caco-2 and C3A cells were used as intestine and liver models to evaluate internalization of Lfs by intestine and liver cells, effects of Lfs on cell proliferation and differentiation, growth of enteropathogenic Escherichia coli (EPEC), chemokine (C-C motif) ligand 20 (CCL20) secretion, and transforming growth factor (TGF)-β1 expression. In addition, HT-29 cells were used as a colon cancer cell model to examine the effects of Lfs on apoptosis.
All Lfs significantly enhanced cell proliferation and differentiation, apoptosis, CCL20 secretion, and TGF-β1 expression. They also markedly suppressed growth of EPEC. Compared with bLf, TLf showed stronger effects on suppression of EPEC growth and enhancement of TGF-β1 secretion, whereas bLf exhibited more potent effects on cell differentiation, apoptosis, and CCL20 secretion.
Our results demonstrate that TLf has several bioactivities similar to human Lf and bLf from milk and may play critical roles in immune and intestinal development in infants as well as having anti-cancer activities in adults. TLf and bLf may be used for different applications owing to their various potencies. TLf may preferentially be used for anti-bacterial applications, whereas bLf may be used for cancer therapy because it exhibits stronger effects on CCL20 secretion, cell differentiation, and apoptosis.
乳铁蛋白（Lf）是一种铁结合糖蛋白，在人乳中含量很高。它是一种多效蛋白，参与多种生物活性，如刺激细胞增殖和分化、免疫功能、抗菌活性、抗感染和抗癌活性。已证明Lf在胃肠道中对蛋白水解有部分抗性，因此在婴儿期可能在肠道和肝脏中发挥重要作用。α-乳运铁蛋白（TLf）是一种重组人Lf，已证明可预防败血症、坏死性小肠结肠炎以及癌症。由于牛Lf（bLf）和人Lf的氨基酸组成不同，且所有三种Lf的糖基化也不同，它们可能具有不同的功能/效力。本研究的目的是研究和比较TLf以及人乳和牛乳中的Lf的生物活性，从而更好地了解不同形式Lf的生物活性及其潜在应用。
在本研究中，使用Caco-2和C3A细胞作为肠道和肝脏模型，以评估Lf被肠道和肝脏细胞内化的情况、Lf对细胞增殖和分化的影响、肠致病性大肠杆菌（EPEC）的生长、趋化因子（C-C基序）配体20（CCL20）的分泌以及转化生长因子（TGF）-β1的表达。此外，使用HT-29细胞作为结肠癌细胞模型，以研究Lf对细胞凋亡的影响。
所有Lf均显著增强细胞增殖和分化、细胞凋亡、CCL20分泌以及TGF-β1表达。它们还显著抑制EPEC的生长。与bLf相比，TLf对抑制EPEC生长和增强TGF-β1分泌的作用更强，而bLf对细胞分化、细胞凋亡和CCL20分泌的作用更显著。
我们的结果表明，TLf具有与来自人乳和牛乳的Lf相似的多种生物活性，可能在婴儿的免疫和肠道发育中发挥关键作用，在成人中也具有抗癌活性。由于TLf和bLf的效力不同，它们可能用于不同的应用。TLf可能优先用于抗菌应用，而bLf可能用于癌症治疗，因为它对CCL20分泌、细胞分化和细胞凋亡表现出更强的作用。
