15-deoxy-Δ 12,14 -prostaglandin J 2 relieved acute liver injury by inhibiting macrophage migration inhibitory factor expression via PPARγ in hepatocyte.

15-deoxy-Δ ^12,14 -prostaglandin J ₂ (15d-PGJ ₂ ) exhibited potential to alleviate liver inflammation in chronic injury but was less studied in acute injury. Acute liver injury was associated with elevated macrophage migration inhibitory factor (MIF) levels in damaged hepatocytes. This study aimed to investigate the regulatory mechanism of hepatocyte-derived MIF by 15d-PGJ ₂ and its subsequent impact on acute liver injury. In vivo, mouse models were established by carbon tetrachloride (CCl ₄ ) intraperitoneal injection, with or without 15d-PGJ ₂ administration. 15d-PGJ ₂ treatment reduced the necrotic areas induced by CCl ₄ . In the same mouse model constructed using enhanced green fluorescent protein (EGFP)-labeled bone marrow (BM) chimeric mice, 15d-PGJ ₂ reduced CCl ₄ induced BM-derived macrophage (BMM, EGFP ⁺ F4/80 ⁺ ) infiltration and inflammatory cytokine expression. Additionally, 15d-PGJ ₂ down-regulated liver and serum MIF levels; liver MIF expression was positively correlated with BMM percentage and inflammatory cytokine expression. In vitro, 15d-PGJ ₂ inhibited Mif expression in hepatocytes. In primary hepatocytes, reactive oxygen species inhibitor (NAC) showed no effect on MIF inhibition by 15d-PGJ ₂ ; PPARγ inhibitor (GW9662) abolished 15d-PGJ ₂ suppressed MIF expression and antagonists (troglitazone, ciglitazone) mimicked its function. In Pparg silenced AML12 cells, the suppression of MIF by 15d-PGJ ₂ was weakened; 15d-PGJ ₂ promoted PPARγ activation in AML 12 cells and primary hepatocytes. Furthermore, the conditioned medium of recombinant MIF- and lipopolysaccharide-treated AML12 respectively promoted BMM migration and inflammatory cytokine expression. Conditioned medium of 15d-PGJ ₂ - or siMif-treated injured AML12 suppressed these effects. Collectively, 15d-PGJ ₂ activated PPARγ to suppress MIF expression in injured hepatocytes, reducing BMM infiltration and pro-inflammatory activation, ultimately alleviating acute liver injury.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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