Effects of cytokines, butyrate and dexamethasone on serum amyloid A and apolipoprotein A-I synthesis in human HUH-7 hepatoma cells.
Serum amyloid A (SAA) and apolipoprotein A-I (apo A-I) are secreted by the liver. As concentrations of both apolipoproteins are inversely related under normal and acute-phase conditions, human HUH-7 hepatoma cells were stimulated with interleukin (IL)-1alpha (100 and 200 U), IL-6 (50 and 100 U), butyrate (2 mM) and dexamethasone (2 x 10(-7)M and 1 x 10(-6)M), alone or in combination. Changes in SAA and apo A-I synthesis were monitored after metabolic labelling of the cells with [35S]-methionine. Intracellular and secreted SAA and apo A-I were immunoprecipitated, separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and the radioactivity in the corresponding bands was counted. Intracellular apolipoprotein levels were increased by all stimuli, either alone or in combination, between 2.7- and 5.5-fold (SAA) and between 2.8- and 4.1-fold (apo A-I), respectively. In a similar manner, apolipoprotein levels secreted by HUH-7 cells were increased between 3.1- and 4.3-fold (SAA) and between 1.9- and 3. 3-fold (apo A-I). Co-administration of cytokines, butyrate and/or dexamethasone had no pronounced synergistic effect on intracellular biosynthesis and secretion of SAA and apo A-I. The results from the present study suggest that apo A-I must not necessarily be considered as a negative acute-phase reactant.
Malle
E
E
Karl-Franzens University Graz, Institute of Medical Biochemistry, Graz, Austria.
Leonhard
B
B
Knipping
G
G
Sattler
W
W
D000210:Acute-Phase Reaction / Q000276:immunology; D016632:Apolipoprotein A-I / Q000096:biosynthesis*; D001053:Apolipoproteins / Q000096:biosynthesis*; D002087:Butyrates / Q000276:immunology* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D003907:Dexamethasone / Q000276:immunology* / Q000494:pharmacology; D005938:Glucocorticoids / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology* / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D002087:Butyrates; D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D003907:Dexamethasone