Title: Amelogenins promote an alternatively activated macrophage phenotype in vitro

Authors: Sofia Almqvist, Maria Werthen, S. Petter Lyngstadaas, Magnus S. Agren, Peter Thomsen

Addresses: Department of Biomaterials, Sahlgrenska Academy, University of Gothenburg, P.O. Box 412, SE-405 30 Goteborg, Sweden; Institute of Biomaterials and Cell Therapy, Box 11119, SE-413 46 Goteborg, Sweden; Molnlycke Health Care AB, Box 13080, SE-402 52 Goteborg, Sweden. ' Institute of Biomaterials and Cell Therapy, Box 11119, SE-413 46 Goteborg, Sweden; Molnlycke Health Care AB, Box 13080, SE-402 52 Goteborg, Sweden. ' Department of Biomaterials, The Dental Faculty, Faculty of Dentistry, University of Oslo, P.O. Box 1109, Blindern, N-0316 Oslo, Norway. ' Department of Surgery K and Copenhagen Wound Healing Center, Bispebjerg Hospital, Copenhagen University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. ' Department of Biomaterials, Sahlgrenska Academy, University of Gothenburg, P.O. Box 412, SE-405 30 Goteborg, Sweden; Institute of Biomaterials and Cell Therapy, Box 11119, SE-413 46 Goteborg, Sweden; BIOMATCELL VINN Excellence Centre of Biomaterials and Cell Therapy, P.O. Box 412, SE-405 30 Goteborg, Sweden

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.

Keywords: amelogenins; extracellular matrix; ECM; monocyte; macrophages; self-assembly; cytokines; tissue repair; tissue regeneration; alternative activation; inflamed tissues; cells; protein aggregates; reparative macrophage phenotype.

DOI: 10.1504/IJNBM.2011.042134

International Journal of Nano and Biomaterials, 2011 Vol.3 No.3, pp.282 - 298

Received: 22 Dec 2010
Accepted: 22 Feb 2011
Published online: 28 Nov 2014 *

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