9-deoxy-delta-9-prostaglandin-d2 and Liver-Cirrhosis

15-Deoxy-Δ(12,14) -Prostaglandin J(2) (15d-PGJ(2) ), a natural peroxisome proliferator-activated receptor gamma (PPAR-γ) ligand, has been implicated as a new antiinflammatory compound with possible clinical applications. Based on this concept, this study was designed to evaluate the effects of 15d-PGJ(2) on bone marrow-derived monocyte/macrophage (BMM) migration, phagocytosis, and cytokine expression after liver injury using mouse models induced by cholestasis or carbon tetrachloride. Mice were lethally irradiated and received bone marrow transplants from enhanced green fluorescent protein transgenic mice. Our results showed that recruitment of BMM was significantly increased during chronic liver injury, and that 15d-PGJ(2) administration reduced BMM, but not neutrophil, dendritic, or T cell migration toward the damaged liver, involving reactive oxygen species generation and independently of PPAR-γ. Moreover, 15d-PGJ(2) inhibited the phagocytic activity of BMM and down-regulated inflammatory cytokine expression in vivo and in vitro. Accordingly, hepatic inflammation and fibrosis were strikingly ameliorated after 15d-PGJ(2) administration.. Our findings strongly suggest the antiinflammation and antifibrogenic potential of 15d-PGJ(2) in chronic liver diseases.

Topics: Analysis of Variance; Animals; Bone Marrow Transplantation; Cell Movement; Cell Proliferation; Cells, Cultured; Chronic Disease; Disease Models, Animal; Flow Cytometry; Fluorescent Antibody Technique; Liver Cirrhosis; Macrophages; Mice; Mice, Transgenic; Phagocytosis; Prostaglandin D2; Random Allocation; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction