Synthesis of Toll-like receptor 4 in Kupffer cells and its role in alcohol-induced liver disease / 中华医学杂志(英文版)

ABSTRACT

<p><b>OBJECTIVES</b>To observe the synthesis of Toll-like receptor (TLR) 4 protein and its mRNA expression in Kupffer cells (KCs) and evaluate the role of TLR 4 in liver injury to rats through alcohol-induced liver disease.</p><p><b>METHODS</b>Twenty-eight Wistar rats were divided into two groups ethanol-fed (group E) and control (group C). Group E rats were given ethanol at a dose of 5 - 12 g x kg(-1) x d(-1), while group C received dextrose. Animals from both groups were killed at 4 and 8 weeks. The KCs were isolated and synthesis of TLR 4 protein was determined by laser scanning confocal microscopy. TLR 4 mRNA expression in KCs was determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. The levels of endotoxin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma were determined. Changes in liver pathology were observed.</p><p><b>RESULTS</b>Laser scanning confocal microscopy showed that the intensity of fluorescence of TLR 4 protein in group E was stronger than group C. Ethanol administration led to a significant increase in TLR 4 mRNA expression in group E compared with group C (P < 0.05). The concentrations of plasma endotoxin, TNF-alpha and IL-6 were higher in group E than in group C (P < 0.05). Liver sections from rats in group E demonstrated marked pathological changes.</p><p><b>CONCLUSION</b>Ethanol administration can lead to the synthesis of TLR 4 protein and its gene expression in KCs, indicating that TLR 4 may play a major role in the development of alcohol-induced liver injury.</p>