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

Abstract:

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 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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Armbrust T,Kreissig M,Tron K,Ramadori G

doi

10.1016/j.jhep.2003.12.013

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

638-45

issue

4

eissn

0168-8278

issn

1600-0641

pii

S0168827803006639

journal_volume

40

pub_type

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