Malondialdehyde–acetaldehyde–protein adducts increase secretion of chemokines by rat hepatic stellate cells
Autor: | Sandra L. Todero, Kusum K. Kharbanda, Michael F. Sorrell, Kris A. Shubert, Dean J. Tuma |
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Rok vydání: | 2001 |
Předmět: |
Male
Chemokine Alcoholic liver disease Health (social science) Chemokine CXCL2 Inflammation Acetaldehyde Toxicology Biochemistry Lipid peroxidation Behavioral Neuroscience chemistry.chemical_compound Malondialdehyde otorhinolaryngologic diseases medicine Animals Rats Wistar Liver Diseases Alcoholic Macrophage inflammatory protein Cells Cultured Chemokine CCL2 Liver injury Dose-Response Relationship Drug biology Drug Synergism Serum Albumin Bovine Chemotaxis General Medicine medicine.disease Molecular biology Rats Liver Neurology chemistry biology.protein Hepatic stellate cell Chemokines medicine.symptom |
Zdroj: | Alcohol. 25:123-128 |
ISSN: | 0741-8329 |
DOI: | 10.1016/s0741-8329(01)00174-4 |
Popis: | Findings obtained from our recent studies have demonstrated that malondialdehyde, a product of lipid peroxidation, and acetaldehyde can react together with proteins in a synergistic manner and form hybrid protein conjugates, which have been designated as malondialdehyde–acetaldehyde (MAA)–protein adducts. These adducts have been detected in livers of ethanol-fed rats and are immunogenic because significant increases in circulating antibody titers against MAA-adducted proteins have been observed in ethanol-fed rats and more recently in human alcoholics. Although immunological factors may tend to perpetuate liver injury, little is known about the direct functional consequences of MAA-adducted proteins on the different cellular populations of the liver. Hepatic stellate cells (HSCs) have been shown to be pivotal in the pathogenesis of fibrosis and in the amplification and self-perpetuation of the inflammatory process. The present study was conducted to determine the effects of MAA-adducted proteins on the function of HSCs. Rat HSCs were exposed to various amounts of MAA–protein adducts and their unmodified controls, and the secretion of two chemokines, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2, that are involved in the chemotaxis of monocytes/macrophages and neutrophils, respectively, was determined. We observed that bovine serum albumin–MAA induced a dose- and time-dependent increase in the secretion of both of these chemokines. These findings indicate that MAA-adducted proteins may play a role in the modulation of the hepatic inflammatory response and could contribute to the pathogenesis of alcoholic liver disease. |
Databáze: | OpenAIRE |
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