Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages.
A culture system that allows human blood monocytes to differentiate into macrophages in vitro was used to study B-cell stimulatory factor-2/interleukin-6 (interferon-beta 2/26 kd protein) expression in mononuclear phagocytes. Using B-cell stimulatory factor-2 (BSF-2) cDNA and a polyclonal, monospecific antibody directed against human BSF-2, we find that strong interleukin-6 (IL-6) expression is initiated in cultured monocytes on stimulation with endotoxin. Maximally induced monocytic BSF-2/IL-6 synthesis (1% to 2% of total proteins secreted by monocytes) is more than ten times stronger than in terminally differentiated macrophages (approximately 0.1% of total secretory proteins). BSF-2/IL-6 mRNA was detectable as early as one hour after stimulation with endotoxin, reaching maximum levels three hours after stimulus. Interleukin-1 (IL-1) was able to stimulate IL-6 synthesis in monocytes, but not in macrophages. Tumor necrosis factor, interferon-gamma and interleukin-2 (IL-2) had no effect on IL-6 synthesis in monocytes or macrophages. We found five molecular weight forms of BSF-2/IL-6 to be secreted by monocytes of 21.5 kd, 23.5 kd, 24 kd, 26 kd, and 28 kd apparent molecular weight. The 26 kd and 28 kd forms were found to represent N-glycosylated molecules, which were not detectable on treatment of the cells with the N-glycosylation inhibitor tunicamycin. The 21.5 kd, 23.5 kd, and 24 kd BSF-2/IL-6 forms were unaffected by tunicamycin treatment. We conclude from our data that cells of the mononuclear phagocyte lineage are one of the main sites of BSF-2/IL-6 (interferon-beta 2/26 kd protein/HSF) synthesis.
Bauer
J
J
Medizinische Klinik, Universität Freiburg, FRG.
Ganter
U
U
Geiger
T
T
Jacobshagen
U
U
Hirano
T
T
Matsuda
T
T
Kishimoto
T
T
Andus
T
T
Acs
G
G
Gerok
W
W
D002454:Cell Differentiation; D002478:Cells, Cultured; D004731:Endotoxins; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis* / Q000302:isolation & purification; D007700:Kinetics; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins