The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers

Cytokine. 1991 May;3(3):231-9. doi: 10.1016/1043-4666(91)90021-5.


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)

MeSH terms

  • 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


  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Concanavalin A
  • Pepsin A
  • Gelatinases
  • Tetradecanoylphorbol Acetate

Associated data

  • SWISSPROT/P14780