ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR-124 upregulation
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Wei Gu1, Lun Yao1, Lexing Li1, Jianping Zhang1, Aaron T. Place2, Richard D. Minshall2,3 and Guoquan Liu1
1Department of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province 430070, P.R. China
2Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
3Department of Anesthesiology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Guoquan Liu, email: firstname.lastname@example.org
Keywords: ICAM-1; miR-124; transcript regulation; macrophage polarization; lung injury
Received: August 05, 2017 Accepted: November 17, 2017 Published: December 05, 2017
Intercellular adhesion molecule-1 is the adhesion molecule mediating leukocyte firm adhesion to endothelial cells, plays a critical role in subsequent leukocyte transmigration. ICAM-1 is also expressed in other cells including macrophages; however, the role of this adhesion molecule in mediating macrophage functions remains enigmatic. We report that ICAM-1 regulates macrophage polarization by positively modulating miR-124 expression. We found higher expression levels of monocyte chemotactic protein-1 in lungs of mice lacking ICAM-1. Consistent with this result, siRNA mediated depletion of ICAM-1 in macrophage resulted in increased expression levels of MCP-1. Moreover, ICAM-1 controlled miR-124 expression and downregulated MCP-1 mRNA and protein expression by binding of miR-124 to MCP-1 3’ untranslated region. ICAM-1 also induced the transcription factor Sp1 expression, which is important for miR-124 expressing in macrophages. Furthermore, ICAM-1 depletion led to M1 macrophage polarization, in contrast, miR-124 mimics promoted M2 macrophage polarization. Exogenous administration of miR-124 mimics into the lungs prevented lipopolysaccharide-induced myeloperoxidase activity in vivo, suggesting that miR-124 is important for dampening acute lung injury. These results collectively show that adhesion molecule ICAM-1 downregulates MCP-1 expression by controlling Sp1 mediated miR-124 levels, which in turn regulate M2 macrophage polarization. Targeting ICAM-1 and downstream miR-124 may present a new therapeutic strategy for acute lung injury.
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