Cathepsin B synthesis by the HL60 promyelocytic cell line: effects of stimulating agents and anti-inflammatory compounds.
Cathepsin B synthesis by the human HL60 promyelocyte cell line was investigated by immunohistochemistry and by the assay of the enzyme in cell lysates using a fluorimetric substrate. HL60 cells were shown to produce cathepsin B in response to treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). Intracellular levels of cathepsin B and immunohistochemical staining of the enzyme were related to time in culture with increasing concentrations of TPA from 1 nmol/1 to 8.0 nmol/1. Synthesis of cathepsin B was associated with TPA-induced phagocytic activity of cells in culture, expression of alpha-naphthyl acetate esterase and reduced cell division. Cathepsin B production was, therefore, related to differentiation of the HL60 promyelocytes into mature macrophage-like cells. Cathepsin B activity in HL60 cell lysates was significantly increased by incubation of the cells with 10 micrograms/ml endotoxin (lipopolysaccharide) from Escherichia coli, but not carrageenan. The production of cathepsin B by TPA-induced HL60 cells was significantly reduced by 0.25 mumol/1 dexamethasone and the non-steroidal anti-inflammatory compound 4-(6-methoxy-2-naphthyl)-butan-2-one but not by indomethacin. The HL60 promyelocytic cell line is a useful model for the study of factors affecting proteinase synthesis by human mononuclear phagocytes.
Burnett
D
D
Crocker
J
J
Afford
S C
SC
Bunce
C M
CM
Brown
G
G
Stockley
R A
RA
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002074:Butanones / Q000494:pharmacology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002351:Carrageenan / Q000494:pharmacology; D002401:Cathepsin B; D002403:Cathepsins / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology*; D009000:Monocytes / Q000201:enzymology*; D000077430:Nabumetone; D010587:Phagocytosis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D002074:Butanones; D004731:Endotoxins; D003907:Dexamethasone; D002351:Carrageenan; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D002403:Cathepsins; D002401:Cathepsin B; D000077430:Nabumetone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin