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

Overview

Journal Histochem Cell Biol

Publisher Springer

Specialties Biochemistry
Cell Biology

Date 2011 Dec 2

PMID 22131058

Citations 14

Authors

Marta Wojcik

Pierluigi Ramadori

Martina Blaschke

Sadaf Sultan

Sajjad Khan

Ihtzaz A Malik

Naila Naz

Gesa Martius

Giuliano Ramadori

Frank C Schultze

Affiliations

Soon will be listed here.

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.

Citing Articles

Disruption of cholangiocyte-B cell crosstalk by blocking the CXCL12-CXCR4 axis alleviates liver fibrosis.

Zhang L, Zhao C, Dai W, Tong H, Yang W, Huang Z Cell Mol Life Sci. 2023; 80(12):379.

PMID: 38010435 PMC: 11072584. DOI: 10.1007/s00018-023-05032-y.

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.

Tu T, Alba M, Datta A, Hong H, Hua B, Jia Y Front Oncol. 2022; 12:958696.

PMID: 36276076 PMC: 9581256. DOI: 10.3389/fonc.2022.958696.

Heparanase Expression Propagates Liver Damage in CCL4-Induced Mouse Model.

Cheng X, Jia J, Zhang T, Zhang X, Vlodavsky I, Li J Cells. 2022; 11(13).

PMID: 35805119 PMC: 9265342. DOI: 10.3390/cells11132035.

The Ameliorative Effects of Saikosaponin in Thioacetamide-Induced Liver Injury and Non-Alcoholic Fatty Liver Disease in Mice.

Chang G, Lin W, Lin T, Liao H, Lu Y Int J Mol Sci. 2021; 22(21).

PMID: 34768813 PMC: 8583725. DOI: 10.3390/ijms222111383.

The Ameliorative Effects of Fucoidan in Thioacetaide-Induced Liver Injury in Mice.

Tsai M, Yang W, Lin C, Wang C, Liu H, Lin C Molecules. 2021; 26(7).

PMID: 33808318 PMC: 8036993. DOI: 10.3390/molecules26071937.

References

Gasparini G, Longo R, Sarmiento R, Morabito A . Inhibitors of cyclo-oxygenase 2: a new class of anticancer agents?. Lancet Oncol. 2003; 4(10):605-15. DOI: 10.1016/s1470-2045(03)01220-8. View

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

Hla T, Neilson K . Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A. 1992; 89(16):7384-8. PMC: 49714. DOI: 10.1073/pnas.89.16.7384. View

Zhang Z, Lai G, Sirica A . Celecoxib-induced apoptosis in rat cholangiocarcinoma cells mediated by Akt inactivation and Bax translocation. Hepatology. 2004; 39(4):1028-37. DOI: 10.1002/hep.20143. View

Proctor E, Chatamra K . High yield micronodular cirrhosis in the rat. Gastroenterology. 1982; 83(6):1183-90. View

Shevchenko A, Wilm M, Vorm O, Mann M . Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 1996; 68(5):850-8. DOI: 10.1021/ac950914h. View

Casado M, Molla B, Roy R, Fernandez-Martinez A, Cucarella C, Mayoral R . Protection against Fas-induced liver apoptosis in transgenic mice expressing cyclooxygenase 2 in hepatocytes. Hepatology. 2007; 45(3):631-8. DOI: 10.1002/hep.21556. View

Yan B, Gong C, Song J, Krausz T, Tretiakova M, Hyjek E . Arginase-1: a new immunohistochemical marker of hepatocytes and hepatocellular neoplasms. Am J Surg Pathol. 2010; 34(8):1147-54. PMC: 3160135. DOI: 10.1097/PAS.0b013e3181e5dffa. View

Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y . Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology. 2005; 129(2):565-76. DOI: 10.1016/j.gastro.2005.05.003. View

10.

Luder C, Algner M, Lang C, Bleicher N, Gross U . Reduced expression of the inducible nitric oxide synthase after infection with Toxoplasma gondii facilitates parasite replication in activated murine macrophages. Int J Parasitol. 2003; 33(8):833-44. DOI: 10.1016/s0020-7519(03)00092-4. View

11.

Knittel T, Dinter C, Kobold D, Neubauer K, Mehde M, Eichhorst S . Expression and regulation of cell adhesion molecules by hepatic stellate cells (HSC) of rat liver: involvement of HSC in recruitment of inflammatory cells during hepatic tissue repair. Am J Pathol. 1999; 154(1):153-67. PMC: 1853435. DOI: 10.1016/s0002-9440(10)65262-5. View

12.

Endo K, Yoon B, Pairojkul C, Demetris A, Sirica A . ERBB-2 overexpression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions. Hepatology. 2002; 36(2):439-50. DOI: 10.1053/jhep.2002.34435. View

13.

Kunkel S, Spengler M, May M, Spengler R, Larrick J, Remick D . Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988; 263(11):5380-4. View

14.

Mansuroglu T, Baumhoer D, Dudas J, Haller F, Cameron S, Lorf T . Expression of stem cell factor receptor c-kit in human nontumoral and tumoral hepatic cells. Eur J Gastroenterol Hepatol. 2009; 21(10):1206-11. DOI: 10.1097/MEG.0b013e328317f4ef. View

15.

Armbrust T, Schwogler S, Zohrens G, Ramadori G . C1 esterase inhibitor gene expression in rat Kupffer cells, peritoneal macrophages and blood monocytes: modulation by interferon gamma. J Exp Med. 1993; 178(2):373-80. PMC: 2191141. DOI: 10.1084/jem.178.2.373. View

16.

Bennett A, Tacca M, Stamford I, ZEBRO T . Prostaglandins from tumours of human large bowel. Br J Cancer. 1977; 35(6):881-4. PMC: 2025548. DOI: 10.1038/bjc.1977.132. View

17.

Knittel T, Armbrust T, Schwogler S, Schuppan D, Ramadori G . Distribution and cellular origin of undulin in rat liver. Lab Invest. 1992; 67(6):779-87. View

18.

Fernandez-Martinez A, Callejas N, Casado M, Bosca L, Martin-Sanz P . Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes. J Hepatol. 2004; 40(6):963-70. DOI: 10.1016/j.jhep.2004.02.019. View

19.

Cordell J, Falini B, Erber W, Ghosh A, Abdulaziz Z, MacDonald S . Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984; 32(2):219-29. DOI: 10.1177/32.2.6198355. View

20.

Kawase H, Fujii K, Miyamoto M, Kubota K, Hirano S, Kondo S . Differential LC-MS-based proteomics of surgical human cholangiocarcinoma tissues. J Proteome Res. 2009; 8(8):4092-103. DOI: 10.1021/pr900468k. View