1. Axl Involved in Mineral Trioxide Aggregate Induces Macrophage Polarization
- Author
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Pei-Hsuan Chen, Chi-Fu Chiang, Yu-Chiao Wu, Hsiao-Wen Yeh, Chi-Chun Su, Shyun-Yeu Liu, Yi-Shing Shieh, Ren-Yeong Huang, and Lu Chou
- Subjects
0301 basic medicine ,THP-1 Cells ,Angiogenesis ,Anti-Inflammatory Agents ,Macrophage polarization ,Neovascularization, Physiologic ,03 medical and health sciences ,0302 clinical medicine ,Phagocytosis ,Proto-Oncogene Proteins ,medicine ,Humans ,Phosphorylation ,Aluminum Compounds ,General Dentistry ,Protein kinase B ,Cells, Cultured ,biology ,Chemistry ,Macrophages ,Silicates ,Monocyte ,NF-kappa B ,Cell Polarity ,Receptor Protein-Tyrosine Kinases ,Oxides ,030206 dentistry ,Transforming growth factor beta ,Calcium Compounds ,Axl Receptor Tyrosine Kinase ,Up-Regulation ,Drug Combinations ,IκBα ,Interleukin 10 ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Cancer research ,Cytokines ,Signal Transduction - Abstract
Introduction In this study, we examined the effect of mineral trioxide aggregate (MTA) on macrophage polarization and the potential involvement of Axl/nuclear factor kappa B (NF-κB) signaling in mediating the effect of MTA. Methods The human monocyte cell line THP-1 was cultured with MTA solution for 1, 2, or 3 days, and the population change of M2 macrophages was analyzed by flow cytometry. Expression of M2 cytokines was examined by enzyme-linked immunosorbent assay. Phagocytosis and angiogenesis-induction ability were also assayed. The involvement of Axl/NF-κB signaling in MTA-treated cells was examined by analyzing phosphorylation status of Axl, Akt, IKKα/β, and IκBα. Specific inhibitors for Axl/Akt/NF-κB signaling were added to MTA-treated THP-1 cells, and their cytokine expression change was examined. Results Flow cytometry analysis showed that MTA treatment increased CD206+ cells in a time-dependent way. After MTA treatment, the expression of M2-related cytokines was up-regulated. MTA also enhanced phagocytic ability and the ability of THP-1 cells to induce angiogenesis. Treatment of MTA led to activate Axl/Akt/NF-kB signal axis by phosphorylation of Axl, Akt, IKKα/β, IκBα, and p65. In addition, MTA-induced interleukin 10, transforming growth factor beta, and vascular endothelial growth factor expression was suppressed as specific inhibitors were added. Conclusions Our findings indicate that MTA is able to induce macrophage polarization toward the M2 phenotype, with up-regulation of interleukin 10, transforming growth factor beta, and vascular endothelial growth factor, and that Axl/Akt/NF-κB signaling participates in this process. These results provide the cellular and molecular basis of MTA's anti-inflammatory action in clinical applications.
- Published
- 2018
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