Abstract

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 12, 14 -prostaglandin J 2 (15d-PGJ 2 ), inhibits bone marrow (BM)-derived macrophage (BMM) migration and inflammatory cytokine production. However, the underlying mechanism of 15d-PGJ 2 inhibited BMM activation is still unclear. Here, we evaluate the role of 15d-PGJ 2 /PPARγ axis in BMM activation. 15d-PGJ 2 reduced activated BMM population in injured livers. Inflammatory cytokine expressions (MIP-1β, TNF-α, NOS2) were depressed by 15d-PGJ 2 in macrophages isolated from treated livers. In vitro, 15d-PGJ 2 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 2 /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 2 /PPARγ axis regulates BMM activation via promoting miR-27b-3p, miR-181a-1-3p, and miR-326-5p expressions. Key messages 15d-PGJ 2 inhibits BMM activation via PPARγ activation. 15d-PGJ 2 /PPARγ axis promotes expression of miR-27b-3p, miR-181a-1-3p, and miR-326-5p. miR-27b-3p, miR-181a-1-3p, and miR-326-5p have an inhibitory effect on BMM activation via 15d-PGJ 2 /PPARγ axis.