Department of Oriental Medicine, Acupuncture and Meridian Science Research Center, Kyung Hee University, Hoegi-dong, Dongdaemoon-gu, Seoul, 130-702, Republic of Korea.
Inflamm Res. 2011 May;60(5):475-82. doi: 10.1007/s00011-010-0294-1. Epub 2010 Dec 16.
Lactoferrin (Lf) is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been defined. In this study, to explain the therapeutic mechanism of Lf, we examined the effect of Lf on endothelial cell activation, leukocyte integration, and angiogenesis in vitro.
Endothelia-leukocyte adhesion assays were used to assess primary cultures of bovine aortic endothelial cells (BAECs) activation following LPS treatment. The mRNA expression of ICAM-1 and proinflammatory cytokines was measured using RT-PCR. Each step of angiogenesis was evaluated in vitro, including endothelial cell proliferation, migration, and tube formation. Proliferation was examined using WST-1 and BrdU incorporation assays, while wound migration assays were used to evaluate cell migration; capillary-like tube formation assays on Matrigel were used to assess tube formation.
Lf reduced the adhesion of human monocyte-like THP-1 cells to BAECs by 45%. Lf also reduced mRNA expression of ICAM-1 and proinflammatory cytokines in BAECs. Lf significantly inhibited BAEC proliferation, migration, and tube formation.
Lf exerted a potent effect on BAEC activation, suggesting that it might function via an endothelia-based mechanism in the treatment of various diseases, including rheumatoid arthritis and cancer.
乳铁蛋白（Lf）具有抗癌和抗炎活性；然而，其治疗机制尚未确定。在这项研究中，为了解释 Lf 的治疗机制，我们研究了 Lf 对体外内皮细胞活化、白细胞整合和血管生成的影响。
采用脂多糖（LPS）处理后的牛主动脉内皮细胞（BAEC）激活的内皮细胞-白细胞黏附试验，评估Lf 对原代培养的 BAEC 的影响。采用 RT-PCR 法检测细胞间黏附分子-1（ICAM-1）和促炎细胞因子的 mRNA 表达。在体外评估了血管生成的每一个步骤，包括内皮细胞增殖、迁移和管状结构形成。采用 WST-1 和 BrdU 掺入试验检测增殖，采用划痕迁移试验检测细胞迁移，采用 Matrigel 上的毛细血管样管状结构形成试验评估管状结构形成。
Lf 使人类单核细胞样 THP-1 细胞与 BAEC 的黏附减少了 45%。Lf 还降低了 BAEC 中 ICAM-1 和促炎细胞因子的 mRNA 表达。Lf 显著抑制了 BAEC 的增殖、迁移和管状结构形成。
Lf 对 BAEC 的激活具有强大的作用，这表明它可能通过基于内皮的机制在治疗各种疾病，包括类风湿关节炎和癌症中发挥作用。
