Modulation of fibronectin gene expression in inflammatory mononuclear phagocytes of rat liver after acute liver injury.
OBJECTIVE
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 CCl(4). 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-beta 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-gamma and lipopolysaccharide could also delay the repair process in the liver. Transforming growth factor-beta may promote liver wound healing after acute liver injury by increasing local cFN synthesis in inflammatory mononuclear phagocytes of the inflammatory infiltrate.
Armbrust
Thomas
T
Georg-August-Universität Göttingen, Abteilung Gastroenterologie und Endokrinologie, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Kreissig
Michael
M
Tron
Kiril
K
Ramadori
Giuliano
G
D000208:Acute Disease; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005353:Fibronectins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D007371:Interferon-gamma; D002251:Carbon Tetrachloride