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miR-27b-3p, miR-181a-1-3p, and miR-326-5p are involved in the inhibition of macrophage activation in chronic liver injury.
- Source :
-
Journal of Molecular Medicine . Oct2017, Vol. 95 Issue 10, p1091-1105. 15p. - Publication Year :
- 2017
-
Abstract
- Macrophages are central players in inflammation, which leads to liver injury. It has been reported that continuous macrophage activation initiates this process. Our previous data show that the anti-inflammatory factor, 15-deoxy-Δ-prostaglandin J (15d-PGJ), inhibits bone marrow (BM)-derived macrophage (BMM) migration and inflammatory cytokine production. However, the underlying mechanism of 15d-PGJ inhibited BMM activation is still unclear. Here, we evaluate the role of 15d-PGJ/PPARγ axis in BMM activation. 15d-PGJ reduced activated BMM population in injured livers. Inflammatory cytokine expressions (MIP-1β, TNF-α, NOS2) were depressed by 15d-PGJ in macrophages isolated from treated livers. In vitro, 15d-PGJ inhibited BMM activation via PPARγ. Moreover, miR-27b-3p, miR-181a-1-3p, and miR-326-5p target MIP-1β, TNF-α, and NOS2 mRNA, respectively. The miRNA expressions were decreased in damaged livers, macrophages isolated from injured livers, and activated BMMs, which were renewed by 15d-PGJ/PPARγ axis. In activated BMMs, the miRNA inhibitors attenuated inhibitory effect of PPARγ agonist (troglitazone or ciglitazone), while replenishing the lack of miRNAs induced by PPARγ deficiency using miRNA mimics caused a decline of inflammatory cytokines. In conclusion, these data suggest that 15d-PGJ/PPARγ axis regulates BMM activation via promoting miR-27b-3p, miR-181a-1-3p, and miR-326-5p expressions. Key messages: [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09462716
- Volume :
- 95
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 125325975
- Full Text :
- https://doi.org/10.1007/s00109-017-1570-0