Studies on the structure and regulation of the human hepatic interleukin-6 receptor.
Affinity cross-linking of 125I-labeled recombinant human interleukin-6 (IL-6) to human hepatoma cells (HepG2) allowed the detection of three IL-6-containing complexes with molecular masses of 100 kDa, 120 kDa and 200 kDa. Treatment of HepG2 cells with dexamethasone led to a time- and dose-dependent up-regulation of IL-6-receptor mRNA levels. By the use of cross-linking this effect was also seen at the protein level, where all three IL-6-binding complexes increased upon incubation of HepG2 cells with dexamethasone. Under conditions of IL-6-receptor up-regulation by dexamethasone, gamma-fibrinogen mRNA induction by IL-6 is stronger and occurs earlier than without dexamethasone. We propose therefore that the expression of the IL-6 receptor might be a rate-limiting step in acute-phase-protein induction.
Rose-John
S
S
Institut für Biochemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Federal Republic of Germany.
Schooltink
H
H
Lenz
D
D
Hipp
E
E
Dufhues
G
G
Schmitz
H
H
Schiel
X
X
Hirano
T
T
Kishimoto
T
T
Heinrich
P C
PC
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000235:genetics; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D003907:Dexamethasone; D005340:Fibrinogen