Amelogenins promote an alternatively activated macrophage phenotype in vitro

Abstract

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.

Critical role for αvβ6 integrin in enamel biomineralization

“…Because amelogenins do not contain any known recognition sites for integrins, it is possible that selfaggregation of amelogenins exposes cryptic integrin recognition sites. Consistently with this hypothesis, amelogenins promote binding of fibroblasts and endothelial cells via multiple integrins, including avb3, avb5 and avb1 (Almqvist et al, 2010;Almqvist et al, 2011). In the present study, ameloblast avb6 integrin did not directly bind to EMD but the cells attached via endogenously deposited matrix.…”

Biological agents and cell therapies in periodontal regeneration

“…In addition, EMPs do not seem to stimulate the monocyte release of pro-inflammatory cytokines (198). Rather, amelogenins seem to support the phenotype of macrophages associated with tissue repair (199). In addition, EMPs may limit the release of pro-inflammatory cytokines from lipopolysaccharide-exposed blood cells (200).…”