Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-γ and IFN-α is reversed by TGF-β in sinusoidal endothelial cells and hepatic mononuclear phagocytes

Autor: Katrin Neubauer, Giuliano Ramadori, Alexander Lindhorst, Bernhard Saile, K. Tron
Rok vydání: 2008
Předmět:
Male
Physiology
medicine.medical_treatment
Down-Regulation
lcsh:Physiology
Flow cytometry
Proinflammatory cytokine
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
Physiology (medical)
medicine
Animals
Immunologic Factors
Interferon gamma
Rats
Wistar
Cell adhesion
Carbon Tetrachloride
Mononuclear Phagocyte System
Cells
Cultured
030304 developmental biology
0303 health sciences
Platelet Endothelial Cell Adhesion Molecule
lcsh:QP1-981
biology
medicine.diagnostic_test
Endothelial Cells
Interferon-alpha
General Medicine
Transforming growth factor beta
Mononuclear phagocyte system
Rats
Cell biology
Cytokine
Gene Expression Regulation
Liver
030220 oncology & carcinogenesis
biology.protein
Cytokines
Chemical and Drug Induced Liver Injury
Research Article
medicine.drug
Zdroj: BMC Physiology
BMC Physiology, Vol 8, Iss 1, p 9 (2008)
ISSN: 1472-6793
DOI: 10.1186/1472-6793-8-9
Popis: Background and aimThe mechanisms of transmigration of inflammatory cells through the sinusoids are still poorly understood. This study aims to identify in vitro conditions (cytokine treatment) which may allow a better understanding of the changes in PECAM (platelet endothelial cell adhesion molecule)-1-gene-expression observed in vivo.Methods and resultsIn this study we show by immunohistochemistry, that there is an accumulation of ICAM-1 (intercellular cell adhesion molecule-1) and ED1 positive cells in necrotic areas of livers of CCl4-treated rats, whereas there are few PECAM-1 positive cells observable. After the administration of CCl4, we could detect an early rise of levels of IFN-γ followed by an enhanced TGF-β protein level. As shown by Northern blot analysis and surface protein expression analysed by flow cytometry, IFN-γ-treatment decreased PECAM-1-gene-expression in isolated SECs (sinusoidal endothelial cells) and mononuclear phagocytes (MNPs) in parallel with an increase in ICAM-1-gene-expression in a dose and time dependent manner. In contrast, TGF-β-treatment increased PECAM-1-expression. Additional administration of IFN-γ to CCl4-treated rats and observations in IFN-γ-/-mice confirmed the effect of IFN-γ on PECAM-1 and ICAM-1-expression observed in vitro and increased the number of ED1-expressing cells 12 h after administration of the toxin.ConclusionThe early decrease of PECAM-1-expression and the parallel increase of ICAM-1-expression following CCl4-treatment is induced by elevated levels of IFN-γ in livers and may facilitate adhesion and transmigration of inflammatory cells. The up-regulation of PECAM-1-expression in SECs and MNPs after TGF-β-treatment suggests the involvement of PECAM-1 during the recovery after liver damage.
Databáze: OpenAIRE
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