Ameloginins promote an alternatively activated macrophage phenotype in vitro

Amelogenins are extracellular matrix proteins used for the topical treatment of chronically inflamed tissues. The influence of amelogenins on human monocyte-derived macrophages was studied by measuring the concentrations of cytokines in culture supernatants. The interactions of cells and protein aggregates were visualised by transmission electron microscopy. The amelogenin treatment of macrophages increased several pro- and anti-inflammatory cytokines, including alternative macrophage activation marker AMAC-1 (p < 0.001) and vascular endothelial growth factor (VEGF; p < 0.001). The levels were independent of cytochalasin B, although amelogenin aggregates were ingested by macrophages. Amelogenin effect was compared with that of tyrosine-rich amelogenin peptide, which apart from augmented VEGF levels (p < 0.05), had no significant influence on the other cytokines analysed. In conclusion, amelogenins increased the macrophage release of key cell mediators involved in tissue repair. The effect was independent of phagocytosis, implying a receptor-mediated signal. The markedly increased levels of AMAC-1 suggest that amelogenins promote a reparative macrophage phenotype.