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MicroRNA-125b-5p modulates the inflammatory state of macrophages via targeting B7-H4

Author:
Diao, Wenli, Lu, Lin, Li, Shan, Chen, Jiangning, Zen, Ke, Li, Limin
Source:
Biochemical and biophysical research communications 2017 v.491 pp. 912-918
ISSN:
0006-291X
Subject:
T-lymphocytes, cell proliferation, cytokines, dexamethasone, genes, macrophages, messenger RNA, protein synthesis, secretion, tissues
Abstract:
As a newly identified negative costimulatory molecule of B7 family, B7-H4 suppresses T cell function via inhibiting cell proliferation and cytokine secretion. Although B7-H4 mRNA is widely distributed in various tissues, its protein expression is strongly limited, suggesting B7-H4 may be regulated post-transcriptionally. However, the mechanism underlying the inducement of B7-H4 expression remains unclear. In the present study, we identified specific targeting sites for miR-125b-5p in the 3′-UTR of B7-H4 gene, and showed that overexpression of miR-125b-5p downregulated B7-H4 expression in macrophages. We also demonstrated that in the activated macrophages, B7-H4 expression could be significantly induced by dexamethasone treatment post-transcriptionally, and that the induction of B7-H4 expression was accomplished by inversely correlated alteration of miR-125b-5p level. Additionally, our data showed that the inflammatory state of macrophages was enhanced by miR-125b-5p at least partially via targeting B7-H4. Taken together, our results demonstrated for the first time that miR-125b-5p could regulate the inflammatory state of macrophages via directly targeting B7-H4.
Agid:
5813795