Overexpression of IL-1ra gene up-regulates interleukin-1β converting enzyme (ICE) gene expression: Possible mechanism underlying IL-1β-resistance of cancer cells

M. Sumitomo, M. Tachibana, M. Murai, M. Hayakawa, H. Nakamura, A. Takayanagi, N. Shimizu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We investigated the interaction of endogenous interleukin (IL)-1β, IL-1ra, and interleukin-1β converting enzyme (ICE) in four human urological cancer cell lines, KU-19-19, KU-1, KU-2 and KU-19-20. Northern blot analysis showed that IL-1β gene was expressed in all call lines. On the other hand, in KU-19-19 and KU-19-20, the gene expressions of both IL-1ra and ICE were suppressed. MTT assay revealed that IL-1β (10 ng ml-1) promoted cell growth in KU-19-19 and KU-19-20, while it inhibited in KU-1 and KU-2. An ICE inhibitor, Acetyl-Tyr-Val-Ala-Asp-CHO (YVAD-CHO) blocked IL-1β-induced growth inhibition in KU-1 and KU-2. Overexpression of the secretory type IL-1ra with adenovirus vector (AxIL-1ra) Enhanced ICE gene expression, while exogenous IL-1ra (100 ng ml-1) did not enhance it. Furthermore, AxIL-1ra treatment promoted endogenous IL-1β secretion and induced significant growth inhibition and apoptotic cell death on KU-19-19 and KU-19-20. Treatment with either IL-1ra (100 ng ml-1), IL-1β antibody (100 μg ml-1), or YVAD-CHO blocked AxlL-1ra-induced cell death in KU-19-19 and KU-19-20. These results suggest that IL-1β-sensitivity depends on the level of ICE gene expression, which is regulated by the level of endogenous sIL-1ra expression. This is a first report on the intracellular junction of sIL-1ra and these findings may provide key insights into the mechanism underlying the viability of cancer cells.

Original languageEnglish
Pages (from-to)277-286
Number of pages10
JournalBritish Journal of Cancer
Volume81
Issue number2
DOIs
Publication statusPublished - 1999

Keywords

  • Adenovirus vector
  • Apoptosis
  • ICE
  • IL-1ra
  • IL-1β

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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