RRC ID 65547
Author Yamamichi K, Fukuda T, Sanui T, Toyoda K, Tanaka U, Nakao Y, Yotsumoto K, Yamato H, Taketomi T, Uchiumi T, Nishimura F.
Title Amelogenin induces M2 macrophage polarisation via PGE2/cAMP signalling pathway.
Journal Arch Oral Biol
Abstract OBJECTIVES:Amelogenin, the major component of the enamel matrix derivative (EMD), has been suggested as a bioactive candidate for periodontal regeneration. Apart from producing a regenerative effect on periodontal tissues, amelogenin has also been reported to have an anti-inflammatory effect. However, the precise molecular mechanisms underlying these effects remain unclear. In the present study, we examined the immunomodulatory effects of amelogenin on macrophages.
DESIGN:Human phorbol 12-myristate 13-acetate (PMA)-differentiated U937 macrophages and CD14+ peripheral blood-derived monocytes (PBMC)-derived macrophages were stimulated with recombinant amelogenin (rM180). After performing a detailed microarray analysis, the effects of rM180 on macrophage phenotype and signal transduction pathways were evaluated by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, confocal microscopy and flow cytometry.
RESULTS:The microarray analysis demonstrated that rM180 increased the expression of anti-inflammatory genes in lipopolysaccharide (LPS)-challenged macrophages after 24h, while it temporarily up-regulated inflammatory responses at 4h. rM180 significantly enhanced the expression of M2 macrophage markers (CD163 and CD206). rM180-induced M2 macrophage polarisation was associated with morphological changes as well as vascular endothelial growth factor (VEGF) production. rM180 enhanced prostaglandin E2 (PGE2) expression, and the activation of the cAMP/cAMP-responsive element binding (CREB) signaling pathway was involved in amelogenin-induced M2 macrophage polarisation. Blocking of PGE2 signaling by indomethacin specifically abrogated rM180 with or without LPS-induced M2 shift in PBMC-derived macrophages.
CONCLUSION:Amelogenin could reprogram macrophages into the anti-inflammatory M2 phenotype. It could therefore contribute to the early resolution of inflammation in periodontal lesions and provide a suitable environment for remodeling-periodontal tissues.
Volume 83
Pages 241-251
Published 2017-11-1
DOI 10.1016/j.archoralbio.2017.08.005
PII S0003-9969(17)30251-0
PMID 28822800
MeSH Amelogenin / pharmacology* Cyclic AMP-Dependent Protein Kinases / physiology* Dinoprostone / physiology* Enzyme-Linked Immunosorbent Assay Flow Cytometry Humans Lipopolysaccharides Macrophages / drug effects* Microarray Analysis Microscopy, Confocal Phenotype Polymerase Chain Reaction Signal Transduction / physiology* Up-Regulation Vascular Endothelial Growth Factor A / metabolism
IF 1.931
Human and Animal Cells U937