Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6.
Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.
Institut für Biochemie, RWTH Aachen, Federal Republic of Germany.
J V
JV
Castell
M J
MJ
Gómez-Lechón
M
M
David
R
R
Fabra
R
R
Trullenque
P C
PC
Heinrich
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000210:Acute-Phase Reaction / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000209:Acute-Phase Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D003907:Dexamethasone; D005340:Fibrinogen; D002097:C-Reactive Protein