論文 - 詳細
| RRC ID | 65547 |
|---|---|
| 著者 | Yamamichi K, Fukuda T, Sanui T, Toyoda K, Tanaka U, Nakao Y, Yotsumoto K, Yamato H, Taketomi T, Uchiumi T, Nishimura F. |
| タイトル | Amelogenin induces M2 macrophage polarisation via PGE2/cAMP signalling pathway. |
| ジャーナル | 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. |
| 巻・号 | 83 |
| ページ | 241-251 |
| 公開日 | 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 |
| リソース情報 | |
| ヒト・動物細胞 | U937 |