Autocrine regulation of collagenase gene expression by TNF-α in U937 cells

Máire M. Callaghan, Rosa M. Lovis, Chidambaram Rammohan, Yang Lu, Richard M. Pope*

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations


Tumor necrosis factor α (TNF-α) has been shown to induce the production of interstitial collagenase by fibroblasts and chondrocytes. We investigated the role of TNF-α in collagenase gene expression by U937 monocyte/macrophage cells. Transcription of the TNF-α gene was observed after 0.5 h of phorbol myristate acetate (PMA) stimulation. Collagenase mRNA expression was not observed until 5-7 h of activation with PMA. TNF-α was detected in the culture supernatants 2-3 h before transcription of the collagenase gene. Neutralization of TNF-α protein with anti-TNF-α antibodies significantly reduced collagenase mRNA expression. Protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibition essentially abolished both PMA-induced TNF-α protein secretion and collagenase mRNA expression. Collagenase gene expression induced by exogenous TNF-α in U937 cells stimulated with a suboptimal concentration of PMA was suppressed by PTK, but not PKC, inhibition. The pyrrolidine derivative of dithiocarbamate, a potent inhibitor of nuclear factor-κB (NF-κB) activation, resulted in a marked reduction in collagenase gene transcription, however, no reduction of TNF-α secretion was noted. Anti-TNF-α antibodies inhibited PMA-induced NF-κB activation. These observations demonstrate an important role for TNF-α in the autocrine regulation of collagenase gene expression by U937 cells. Additionally, TNF-α-induced PTK and NF-κB activation were important in collagenase gene expression in this cell line.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalJournal of Leukocyte Biology
Issue number1
StatePublished - Jan 1996


  • Gene regulation
  • Myelomonocytic cells
  • Self-regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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