TableEdit

Van Ranst, M, Norga, K, Masure, S, Proost, P, Vandekerckhove, F, Auwerx, J, Van Damme, J and Opdenakker, G (1991) The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers. Cytokine 3:231-9

The induction of proteolytic enzymes is an important mechanism in the migration of monocytes into tissues and body fluids. The monocytic cell line THP-1 was used as a model system to study the production of a particular gelatinase. Upon stimulation with phorbol myristate acetate (PMA) the cells differentiated to the adherent phenotype and produced significant amounts of a 96-kD gelatinase in a dose-dependent way. The secretion rate was maximal between 12 and 24 h after induction. Study of gelatinase mRNA steady state levels showed that the synthesis of THP-1 gelatinase is regulated by PMA at transcriptional or posttranscriptional levels. Stimulation of signal transduction pathways with other substances, including calcium ionophore A 23187, dibutyryl cyclic AMP, and dexamethasone, were ineffective in inducing gelatinase mRNA or enzyme activity. However, THP-1 cells were responsive to the cytokine interleukin (IL)-1 beta, to bacterial lipopolysaccharide (LPS), and the lectin concanavalin A (Con A), the kinetics of gelatinase induction being similar to those of induction by PMA. The THP-1 cells did not synthesize and/or secrete detectable levels of IL-6 after stimulation with PMA, Con A, LPS, or IL-1 beta. The 96-kD monocytic THP-1 gelatinase was shown to be a neutral metalloproteinase that cross-reacted with hepatoma-derived and neutrophil gelatinases in immunoprecipitation experiments. The active enzyme produced by THP-1 cells consistently showed, however, a molecular mass different from that of normal granulocyte-, monocyte-, and tumor cell-derived gelatinases.(ABSTRACT TRUNCATED AT 250 WORDS)

PubMed

Amino Acid Sequence; Carcinoma, Hepatocellular; Cell Differentiation/drug effects; Cell Line; Concanavalin A/pharmacology; Gelatinases; Gene Expression Regulation, Enzymologic/drug effects; Gene Expression Regulation, Neoplastic/drug effects; Humans; Interleukin-1/pharmacology; Kinetics; Leukemia, Monocytic, Acute; Lipopolysaccharides/pharmacology; Liver Neoplasms; Molecular Sequence Data; Molecular Weight; Pepsin A/genetics; Pepsin A/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Signal Transduction/drug effects; Tetradecanoylphorbol Acetate/pharmacology; Transcription, Genetic/drug effects