Ethanol Feeding Potentiates the Pro-Inflammatory Response of Kupffer Cells to Cellular Fibronectin

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2011-04, Vol.35 (4), p.717-725
• Main Authors: Aziz-Seible, Razia S., Lee, Serene M., Kharbanda, Kusum K., McVicker, Benita L., Casey, Carol A.
• Format: Article
• Language: English
• Subjects: Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Caspase 3 - metabolism; Cell Culture Techniques; Cell Survival - drug effects; Cellular Fibronectin; Central Nervous System Depressants - metabolism; Central Nervous System Depressants - pharmacology; Central Nervous System Depressants - toxicity; Ethanol; Ethanol - metabolism; Ethanol - pharmacology; Ethanol - toxicity; Extracellular Matrix - physiology; Fibronectins - physiology; Inflammation - chemically induced; Inflammation - physiopathology; Interleukin-6 - metabolism; Kupffer Cells; Kupffer Cells - cytology; Kupffer Cells - drug effects; Kupffer Cells - pathology; Kupffer Cells - physiology; Liver - cytology; Liver - physiopathology; Male; Matrix Metalloproteinase 2; Medical sciences; Rats; Rats, Wistar; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Toxicology; Tumor Necrosis Factor-alpha
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2010.01389.x

Background:  Excessive alcohol consumption leads to the increased extracellular matrix deposition of cellular fibronectin (cFn) in the liver, which is also implicated as an initiating event in the fibrogenic process. We propose that cFn directly stimulates Kupffer cells (KCs), which are involved in the early response to tissue damage, to produce factors that enhance the progression of alcohol‐induced liver injury toward inflammation and fibrosis. Method:  KCs were isolated from rats fed a control or ethanol liquid diet for 4 to 6 weeks. The effect of exogenous cFn on KC viability and the secretion of the cytokines, TNF‐α and IL‐6, as well as of matrix remodeling factors, MMP‐2 and TIMP‐2, was determined after 20 hours of cell culture. Results:  For KCs from both control‐ and ethanol‐fed rats, viability remained unaffected by treatment with cFn. TNF‐α and IL‐6 production were increased in KCs exposed to cFn, with cells treated with 1, 2.5, and 5 μg/ml cFn secreting significantly higher levels of both cytokines compared with untreated cells (p