Heterogeneous modulation of acute-phase-reactant mRNA levels by interleukin-1 beta and interleukin-6 in the human hepatoma cell line PLC/PRF/5.
The acute-phase response to tissue injury and inflammation is accompanied by a dramatic increase in the hepatic synthesis of plasma proteins known as acute-phase reactants (APRs). This response is mediated by cytokines produced in part by activated macrophages at the site of inflammation; glucocorticoids have also been implicated as playing a regulatory role. The effects of the cytokines interleukin (IL)-1 beta and -6, alone or in combination, and in the absence or presence of the synthetic glucocorticoid dexamethasone, on the levels of APR mRNAs in the human hepatoma cell line PLC/PRF/5 were analysed. The accumulation of APR mRNAs [the complement components C3, factor B and Cl inhibitor; the major APRs C-reactive protein (CRP) and serum amyloid A protein and the CRP analogue serum amyloid P protein] was determined in dose-response and time-course studies. The APRs differed from each other in their responses to IL-1 beta alone, IL-6 alone, and IL-1 beta plus IL-6. Dexamethasone enhanced the cytokine-driven induction of a subset of APR mRNAs. These studies detail the heterogeneity of the 'in vitro' acute-phase response to defined mediators.
Steel
D M
DM
Division of Immunology, Children's Hospital, Boston, MA.
Whitehead
A S
AS
D000209:Acute-Phase Proteins / Q000235:genetics*; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D015342:DNA Probes; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology
D000209:Acute-Phase Proteins; D015342:DNA Probes; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D003907:Dexamethasone