Interleukin-1β secreted from monocytic cells induces the expression of matrilysin in the prostatic cell line LNCaP

Russell D. Klein, Alexander H. Borchers, Padma Sundareshan, Catherine Bougelet, Matthew R. Berkman, Raymond B. Nagle, G. Tim Bowden

Research output: Contribution to journalArticle

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Abstract

Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of epithelial origin and in normal tissues during events involving matrix remodeling such as the cycling endometrium. We previously observed that inflamed ductule and acinar epithelia in the prostate also overexpress matrilysin. The presence of infiltrating macrophages in these areas prompted us to determine if factors secreted from monocytes could induce matrilysin expression in a human prostatic cell line. Conditioned media collected from the monocyte cell line THP-1 following lipopolysaccharide treatment substantially induced matrilysin protein and mRNA expression in LNCaP prostate carcinoma cells. Matrilysin expression in LNCaP cells was also induced by recombinant interleukin (IL)-1 (50 pM), but not by equimolar concentrations of recombinant tumor necrosis factor-α or IL-6. The matrilysin-inducing activity of THP-1 conditioned medium was completely abrogated by preincubation with a neutralizing antibody to IL-1β. Transient transfection analyses with a chimeric human matrilysin promoter- chloramphenicol acetyltransferase reporter construct demonstrated that IL- 1β activates transcription through the matrilysin promoter in LNCaP cells. This is the first report of matrilysin induction by an inflammatory cytokine in a cell line of epithelial origin, and the results suggest a potential mechanism for the overexpression of matrilysin in inflamed ducts and glands of the prostate.

Original languageEnglish (US)
Pages (from-to)14188-14192
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number22
DOIs
StatePublished - May 30 1997

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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