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ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR-124 upregulation

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journal contribution
posted on 19.06.2018 by Wei Gu, Lun Yao, Lexing Li, Jianping Zhang, Aaron T. Place, Richard D. Minshall, Guoquan Liu
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.

Funding

The work is supported by National Natural Science Foundation of China (NSFC) (No. 31372418, GL.), Huazhong Agricultural University Scientific & Technology Self-innovation Foundation (program No. 2012RC011, G.L.), the 948 Project of Chinese Ministry of Agriculture (2015-Z33, GL). NIH grants RO1 HL71626 and P01 HL60678 (RM). We thank Dr. S. Reddy, University of Illinois at Chicago, for critical reading of the manuscript.

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Citation

Gu, W., Yao, L., Li, L., Zhang, J., Place, A. T., Minshall, R. D. and Liu, G. ICAM-1 regulates macrophage polarization by suppressing MCP- 1 expression via miR-124 upregulation. Oncotarget. 2017. 8(67): 111882-111901. 10.18632/oncotarget.22948.

Publisher

Impact Journals

Language

en_US

issn

1949-2553

Issue date

05/12/2017

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