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 Udayakumar, Raymond B. Nagle, George Timothy Bowden

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 - 2001
Externally publishedYes

Fingerprint

NF-kappa B
Interleukin-1
Prostate
Interleukin-6
Carcinoma
Cell Line
Matrix Metalloproteinase 7
Transcriptional Activation
Messenger RNA
Proteins
promatrilysin
Transfection
Lipopolysaccharides
Monocytes

Keywords

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

ASJC Scopus subject areas

  • Cancer Research

Cite this

Interleukin-1β-induced promatrilysin expression is mediated by NFκB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP1. / Maliner-Stratton, Mimi Suzanne; Klein, Russell D.; Udayakumar, Thirupandiyur; Nagle, Raymond B.; Bowden, George Timothy.

In: Neoplasia, Vol. 3, No. 6, 2001, p. 509-520.

Research output: Contribution to journalArticle

Maliner-Stratton, Mimi Suzanne ; Klein, Russell D. ; Udayakumar, Thirupandiyur ; Nagle, Raymond B. ; Bowden, George Timothy. / Interleukin-1β-induced promatrilysin expression is mediated by NFκB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP1. In: Neoplasia. 2001 ; Vol. 3, No. 6. pp. 509-520.
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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.",
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AU - Bowden, George Timothy

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AB - 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.

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