title: Immunodetection of cyclooxygenase-2 (COX-2) is restricted to tissue macrophages in normal rat liver and to recruited mononuclear phagocytes in liver injury and cholangiocarcinoma.
abstract: It has been suggested that cyclooxygenase-2 (COX-2)-mediated prostaglandin synthesis is associated with liver inflammation and carcinogenesis. The aim of this study is to identify the cellular source of COX-2 expression in different stages, from acute liver injury through liver fibrosis to cholangiocarcinoma (CC). We induced in rats acute and "chronic" liver injury (thioacetamide (TAA) or carbon tetrachloride (CCl(4))) and CC development (TAA) and assessed COX-2 gene expression in normal and damaged liver tissue by RT-PCR of total RNA. The cellular localization of COX-2 protein in liver tissue was analyzed by immunohistochemistry as well as in isolated rat liver cells by Western blotting. The findings were compared with those obtained in human cirrhotic liver tissue. The specificity of the antibodies was tested by 2-DE Western blot and mass spectrometric identification of the positive protein spots. RT-PCR analysis of total RNA revealed an increase of hepatic COX-2 gene expression in acutely as well as "chronically" damaged liver. COX-2-protein was detected in those ED1(+)/ED2(+) cells located in the non-damaged tissue (resident tissue macrophages). In addition COX-2 positivity in inflammatory mononuclear phagocytes (ED1(+)/ED2(-)), which were also present within the tumoral tissue was detected. COX-2 protein was clearly detectable in isolated Kupffer cells as well as (at lower level) in isolated "inflammatory" macrophages. Similar results were obtained in human cirrhotic liver. COX-2 protein is constitutively detectable in liver tissue macrophages. Inflammatory mononuclear phagocytes contribute to the increase of COX-2 gene expression in acute and chronic liver damage induced by different toxins and in the CC microenvironment.
authors: Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
authors: Marta
authors: M
authors: Wójcik
authors: Pierluigi
authors: P
authors: Ramadori
authors: Martina
authors: M
authors: Blaschke
authors: Sadaf
authors: S
authors: Sultan
authors: Sajjad
authors: S
authors: Khan
authors: Ihtzaz A
authors: IA
authors: Malik
authors: Naila
authors: N
authors: Naz
authors: Gesa
authors: G
authors: Martius
authors: Giuliano
authors: G
authors: Ramadori
authors: Frank C
authors: FC
authors: Schultze
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006505:Hepatitis / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D010586:Phagocytes / Q000378:metabolism*; D051381:Rats
chemical_list: D051546:Cyclooxygenase 2