Interleukin-1β-induced promatrilysin expression is mediated by NFκB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP1

Mimi Suzanne Maliner-Stratton, Russell D. Klein, Thirupandiyur S. Udayakumar, Raymond B. Nagle, George Timothy Bowden

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Previously, our laboratory showed that interleukin-1β (IL-1β) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1β-induced promatrilysin expression is mediated by an indirect mechanism that requires nuclear factor Kappa B (NFκB)-dependent synthesis of IL-6. Inhibition of protein synthesis with cyclohexamide blocked IL-1β-mediated induction of matrilysin mRNA suggesting that synthesis of one or more additional factors is required for IL-1β-induced promatrilysin protein expression. Blockage of NFκB transactivation activity abrogated IL-1β-induced promatrilysin expression to baseline levels suggesting that NFκB transactivation activity is necessary. Inhibition of IL-6 activity attenuated IL-1β-induced promatrilysin, but not NFκB transactivation activity indicating that IL-6 acts downstream of NFκB in potentiation of IL-1β-mediated promatrilysin expression. Inhibition of protein synthesis with cyclohexamide did not alter IL-6-induced induction of matrilysin mRNA indicating that, contrary to the mechanism by which IL-1β regulates promatrilysin expression, IL-6-mediated matrilysin mRNA expression does not require new protein synthesis. Transient transfection with dominant negative STAT3 inhibited IL-1β- and IL-6-induced promatrilysin. These data provide evidence that NFκB-mediated IL-6 synthesis is required for IL-1β-induced promatrilysin expression, and IL-6 signaling through STAT3 plays a role in IL-1β-induced promatrilysin expression.

Original languageEnglish (US)
Pages (from-to)509-520
Number of pages12
JournalNeoplasia
Volume3
Issue number6
DOIs
StatePublished - Jan 1 2001

Keywords

  • Interleukin-1
  • Interleukin-6
  • Matrilysin
  • Matrix metalloproteinase
  • Prostate

ASJC Scopus subject areas

  • Cancer Research

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