Title |
Activation of Adhesion GPCR EMR2/ADGRE2 Induces Macrophage Differentiation and Inflammatory Responses via Gα16/Akt/MAPK/NF-κB Signaling Pathways
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Published in |
Frontiers in immunology, April 2017
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DOI | 10.3389/fimmu.2017.00373 |
Pubmed ID | |
Authors |
Kuan-Yu I, Yi-Shu Huang, Ching-Hsun Hu, Wen-Yi Tseng, Chia-Hsin Cheng, Martin Stacey, Siamon Gordon, Gin-Wen Chang, Hsi-Hsien Lin |
Abstract |
EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor critically implicated in vibratory urticaria, a rare type of allergy caused by vibration-induced mast cell activation. In addition, EMR2 is also highly expressed by monocyte/macrophages and has been linked to neutrophil migration and activation. Despite these findings, little is known of EMR2-mediated signaling and its role in myeloid biology. In this report, we show that activation of EMR2 via a receptor-specific monoclonal antibody promotes the differentiation of human THP-1 monocytic cell line and induces the expression of pro-inflammatory mediators, including IL-8, TNF-α, and MMP-9. Using specific signaling inhibitors and siRNA knockdowns, biochemical and functional analyses reveal that the EMR2-mediated signaling is initiated by Gα16, followed by the subsequent activation of Akt, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells. Our results demonstrate a functional role for EMR2 in the differentiation and inflammatory activation of human monocytic cells and provide potential targets for myeloid cell-mediated inflammatory disorders. |
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Unknown | 2 | 50% |
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Scientists | 1 | 25% |
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Other | 5 | 15% |
Student > Ph. D. Student | 5 | 15% |
Student > Master | 2 | 6% |
Researcher | 2 | 6% |
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Unknown | 10 | 29% |
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Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Other | 2 | 6% |
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