Effect of cytokines on glycosylation of acute phase proteins in human hepatoma cell lines.
The effects of various cytokines on synthesis and microheterogeneity of carbohydrate structure of alpha 1-proteinase inhibitor (PI) and alpha-fetoprotein (AFP) in the human hepatoma cell lines Hep 3B and Hep G2 were studied. In both lines, crude cytokine preparations from LPS-activated human monocytes (CM) and several cell lines led to increased PI and decreased AFP synthesis, while recombinant interleukin 1 (IL-1), recombinant tumor necrosis factor (TNF) and hepatocyte stimulating factor preparations (HSF) affected AFP but not PI production. Several of the crude cytokine preparations, but not IL-1, TNF, or HSF, caused Hep 3B cells to secrete forms of PI and AFP showing increased reactivity with Con A upon testing by affinity electrophoresis, while decreased reactivity with Con A was seen in these proteins secreted by Hep G2 cells. Determination of molecular size of PI inducing activity in CM showed a sharp peak at about 17 kD while AFP inhibiting activity was present in a very broad range of molecular size fractions maximal at 17-30 kD. Changes in patterns of glycosylation of these proteins were attributable to cytokines of about 30 kD in Hep 3B and 44 kD in Hep G2 cells. These findings demonstrate the existence of a family of glycosylation regulating cytokines, and suggest that distinct mechanisms within hepatocytes, responsive to different cytokines, may lead to increased or decreased Con A binding of glycoproteins and to altered gene expression.
Mackiewicz
A
A
Department of Immunology and Rheumatology, Academy of Medicine, Poznan, Poland.
Schultz
D
D
Mathison
J
J
Ganapathi
M
M
Kushner
I
I
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D001798:Blood Proteins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D006031:Glycosylation; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000515:alpha 1-Antitrypsin; D000509:alpha-Fetoproteins / Q000096:biosynthesis
D000209:Acute-Phase Proteins; D001798:Blood Proteins; D015850:Interleukin-6; D007378:Interleukins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D000509:alpha-Fetoproteins; D003208:Concanavalin A