Modulation of fibronectin gene expression in inflammatory mononuclear phagocytes of rat liver after acute liver injury

Background/Aims: In acute liver injury, fibronectin (FN) is deposited at the site of hepatocellular necrosis. We have previously shown that liver inflammatory mononuclear phagocytes (MNP), in contrast to quiescent hepatic macrophages, synthesize abundant amounts of FN. We now analyzed effects of agents known to influence macrophage functions to better understand liver damage and repair. Methods: Acute rat liver injury was induced by CCl4. Liver cellular FN (cFN) expression was analyzed by in situ-hybridization. Liver MNP were isolated and characterized immunocytochemically. Protein synthesis was studied by biosynthetic labeling, immunoprecipitation, and SDS-PAGE. RNA was analyzed by Northern Blotting. Results: cFN gene expression was localized by in situ-hybridization and immunohistochemistry within the pericentral inflammatory infiltrate. Treatment of inflammatory MNP with dexamethasone, or interferon-gamma, or lipopolysaccharide induced a dose-dependent decrease in cFN gene expression, whereas transforming growth factor-β increased cFN gene expression. Conclusions: 1. Inflammatory MNP express cFN. 2. Downregulation of cFN expression by dexamethasone in inflammatory MNP may explain delayed wound healing after corticosteroid therapy. Interferon-γ and lipopolysaccharide could also delay the repair process in the liver. Transforming growth factor-β may promote liver wound healing after acute liver injury by increasing local cFN synthesis in inflammatory mononuclear phagocytes of the inflammatory infiltrate.