Activation of Adhesion GPCR EMR2/ADGRE2 Induces Macrophage Differentiation and Inflammatory Responses via G alpha(16)/Akt/MAPK/NF-kappa B Signaling Pathways

作者：I Kuan Yu; Huang Yi Shu; Hu Ching Hsun; Tseng Wen Yi; Cheng Chia Hsin; Stacey Martin; Gordon Siamon; Chang Gin Wen; Lin Hsi Hsien

来源：Frontiers in Immunology, 2017, 8: 373.

DOI：10.3389/fimmu.2017.00373

• cytokine
• EMR2
• GPCR
• macrophage
• inflammation
• signaling

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-alpha, and MMP-9. Using specific signaling inhibitors and siRNA knockdowns, biochemical and functional analyses reveal that the EMR2-mediated signaling is initiated by G alpha(16), 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.

• 出版日期2017-4-3
• 单位长春大学