Action of recombinant human interleukin 6, interleukin 1β and tumor necrosis factor α on the mRNA induction of acute‐phase proteins

摘要

AbstractThe rat hepatoma cell line Fao was used to study the role of three inflammatory mediators on the mWA regulation of several acute‐phase proteins. In the presence of 10−6M dexamethasone β‐fibrinogen mRNA levels increased 6‐fold after addition of recombinant human IL6 (rhIL6). rhIL1β or recombinant human tumor necrosis factor a (rhTNFα) had essentially no effect on β‐fibrinogen mRNA induction but led to a 20‐fold increase in α1‐acid glycoprotein mRNA in the presence of dexamethasone. On the other hand, rhIL6 was a much weaker stimulator of α1‐acid glycoprotein mRNA synthesis. All three mediators reduced albumin mRNA concentrations to about 30 of controls.Whereas the induction of β‐fibrinogen mRNA was potentiated by dexamethasone, the synthetic glucocorticoid analog was an absolute requirement for the stimulation of αl‐acid glycoprotein mRNA. The mRNA levels of the negative acute‐phase protein albumin were induced 5‐fold by dexamethasone alone. The β‐fibrinogen mRNA induction started immediately after addition of rhIL6 and reached a maximum between 12 and 18 h. In contrast, the time‐course for α1‐acid glycoprotein mRNA synthesis showed a lag phase of 8 h followed by an increase up to 20 h after rhIL 1β. RhTNFα led to an even more delayed increase in αl‐acid glycoprotein mRNA. Whereas in the case of β‐fibrinogen mRNA induction no synergistic effect was observed between various concentrations of the three mediators, the combination of rhIL6/rhIL1β as well as rhIL6/rhTNFα or rhIL 1β/rhTNFα regulated synergistically α1‐acid glycoprotein and albumin mRNA. It is concluded that discrete acute‐phase proteins are regulated differently by the inflammatory mediators IL6, IL1β and TNFα, indicating that the acute‐phase response is more complex than previously assumed.The Fao cell line used in this study turned out to be an ideal model for acute‐phase protein regulation, suitable for the disc