Document Detail


Endotoxin exacerbates immunologically induced liver injury in cooperation with interferon-gamma.
MedLine Citation:
PMID:  11131296     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE AND DESIGN: To investigate the role of endotoxin in the development of immunologically induced liver injury. MATERIALS AND METHODS: A new model of liver injury induced in BALB/c mice by delayed-type hypersensitivity to picryl chloride and its in vitro assay for the interaction between liver nonparenchymal and parenchymal cells were used. RESULTS: Plasma endotoxin in the injured liver correlated well with serum alanine transaminase (ALT) activity (r = 0.601). Tolerance to lipopolysaccharide led to a significant inhibition of serum ALT elevation. However, lipopolysaccharide in vitro increased the ALT release from hepatocytes caused by nonparenchymal cells only in the presence of IFN-gamma. When nonparenchymal cells were separated into Kupffer and non-Kupffer cell populations, the synergistic hepatotoxicity of lipopolysaccharide and IFN-gamma was still observed in the former but not in the latter cell type. Lipopolysaccharide with IFN-gamma also enhanced TNF-alpha levels. Anti-TNF-alpha almost completely inhibited the ALT release. Combined use of TNF-alpha and IFN-gamma caused marked hepatocyte damage, while these cytokines alone did not. CONCLUSIONS: We suggest that elevated endotoxin levels accompanying the development of liver injury may activate Kupffer cells to release TNF-alpha leading to exacerbation of hepatocyte damage in cooperation with IFN-gamma produced during liver injury.
Authors:
X Chen; J Cao; Q Xu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Inflammation research : official journal of the European Histamine Research Society ... [et al.]     Volume:  49     ISSN:  1023-3830     ISO Abbreviation:  Inflamm. Res.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-22     Completed Date:  2001-03-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9508160     Medline TA:  Inflamm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  571-7     Citation Subset:  IM    
Affiliation:
Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, Nanjing, The People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / biosynthesis,  blood
Animals
Cells, Cultured
Drug-Induced Liver Injury*
Endotoxins / blood,  physiology*
Female
Hepatocytes / drug effects,  immunology
Hypersensitivity, Delayed / blood,  chemically induced*,  immunology*
Interferon-gamma / pharmacology*
Kupffer Cells / immunology
Lipopolysaccharides / pharmacology
Liver / cytology,  drug effects,  immunology
Liver Diseases / blood,  immunology*
Mice
Mice, Inbred BALB C
Nitric Oxide / biosynthesis,  immunology
Picryl Chloride / pharmacology
Tumor Necrosis Factor-alpha / biosynthesis,  immunology
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 82115-62-6/Interferon-gamma; 88-88-0/Picryl Chloride; EC 2.6.1.2/Alanine Transaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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