Activation of Adhesion GPCR EMR2/ADGRE2 Induces Macrophage Differentiation and Inflammatory Responses via Gα16/Akt/MAPK/NF-κB Signaling Pathways

Journal article

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

Authors: I, K-Y; Huang, Y-S; Hu, C-H; Tseng, W-Y; Cheng, C-H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Frontiers Media
• Journal: Frontiers in Immunology
• Volume: 8
• Pages: 373-373
• Publication date: 2017-04-03
• DOI: 10.3389/fimmu.2017.00373
• EISSN: 1664-3224
• ISSN: 1664-3224
• Language: English
• Keywords: Cell biology; Protein kinase B; NF-κB; Biology; Myeloid; Cancer research; MAPK/ERK pathway; Chemistry; Inflammation; Immunology; Signal transduction