Advanced glycation end products (AGEs) are the potential inflammatory molecules produced by non-enzymatic glycation reaction between reducing sugar and amine residues on biomolecules, and have been suggested to be involved in various age-related diseases. AGEs stimulate the pattern recognition receptors (TLR4, TLR2, RAGE) on immune cells such as macrophages and vascular endothelial cells, and are involved in chronic inflammation and tissue remodeling, Therefore, it is thought that regulation of AGEs-induced inflammatory responses can be an important therapeutic target for prevention and treatment of age-related diseases. In previous studies, we found that AGEs and lactoferrin (Lf) can interact with high affinity. Based on this finding, it was examined the effect of AGEs-Lf interaction on TNF-α mRNA expression in macrophage in this study. For this purpose, we initially made the triple KO macrophage cell line which lacked three receptors (TLR4, TLR2 and RAGE) by genome editing. When this triple KO strain was stimulated with Lf (10 μg/mL), it was shown that the increase in expression of TNF-α mRNA expression. On the other hand, this stimulation was significantly suppressed by co-addition of AGEs (1,000 μg/mL). From these findings, it was suggested that AGEs interact with Lf with high affinity, and they are involved in the pathogenesis of tissue remodeling.