Effects of ethanol on prostanoid production by liver fat-storing cells

Abstract

Fat-storing cells participate in the development of alcoholic liver disease. To study possible effects of ethanol on prostaglandin metabolism by fat-storing cells, we isolated them from normal rat liver. Cultured fat-storing cells produced substantial amounts (DNA, about 2 ng/micrograms every 24 hr) of prostaglandin E2 and prostaglandin I2 (measured as 6-keto prostaglandin F1 alpha) but no significant amounts of prostaglandin F2 alpha. This production was markedly enhanced by the addition of ethanol in concentrations likely to occur in the blood during alcohol consumption. We confirmed the presence of class 1 alcohol dehydrogenase activity and isoenzymes in the cytosol of cultured fat-storing cells in their second passage. The stimulatory effect of ethanol was inhibited by 4-methylpyrazole (an alcohol dehydrogenase inhibitor), exaggerated by disulfiram (an aldehyde dehydrogenase inhibitor) and reproduced by concentrations of acetaldehyde likely to occur in the liver. Thus, our results indicate that fat-storing cells produce vasodilatory prostaglandins and that this production is enhanced by the acetaldehyde that results from the oxidation of ethanol catalized by alcohol dehydrogenase present in these cells.

Hepatic stellate cells – from past till present: morphology, human markers, human cell lines, behavior in normal and liver pathology

“…In vivo , this evidence has a particular importance due to the vicinity of stellate cells to nerve terminations in healthy liver [ 2 ]. In response to ethanol stimulation, HSCs become intensively activated and secrete PGI 2 and PGE 2 [ 206 ]. HSCs also secrete leukotriene C 4 and B 4 [ 207 ].…”

Transforming Growth Factor-β1 as a Surrogate Marker of Hepatic Dysfunction in Chronic Liver Diseases

“…Hepatocyte injury is responsible for the release of numerous cytokines, including TGF-β 1 , which plays a principal role in the activation of fat-storing (Ito) cells. Their transformation into myofibroblasts is an essential step in the initiation of liver fibrosis (2)(3)(4). Long-lasting stimulation of fat-storing cells, resulting from continuous hepatocyte injury and superabundance of profibrogenic factors such as TGF-β 1 , can lead to the development of liver cirrhosis.…”

Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells

“…aHSCs also produce prostaglandins such as prostaglandin I 2 (PGI2) and PGE2, which promote macrophage activation by regulating intracellular cyclic adenosine monophosphate (cAMP) levels. 122 Factors like macrophage colony-stimulating factor (M-CSF) 123 and monocyte chemoattractant protein-1 (MCP-1) 124 produced by aHSCs regulate the accumulation and growth of macrophages within the inflammatory milieu of FLD. In addition, aHSCs contribute to neutrophil chemotaxis and activation by secreting platelet-activating factor (PAF), further amplifying neutrophil-driven inflammatory responses in the damaged liver.…”