Cytocidal effect of interleukin 1 (IL-1) on HeLa cells is mediated by both soluble and transmembrane tumor necrosis

Małgorzata Doszczak1, Arkadiusz Pierzchalski1, Jolanta Grzenkowicz1

  • 1Cell Biology Unit, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-210 Gdańsk, Poland.

Cytokine
|April 5, 2008
PubMed

Insights

Interleukin 1 (IL-1) induces cell death in HeLa cells via tumor necrosis factor (TNF). This study reveals IL-1 cytotoxicity is an indirect effect mediated by both soluble and transmembrane TNF.

Area of Science:

  • Immunology
  • Cell Biology
  • Cytokine Signaling

Background:

  • Interleukin 1 (IL-1) is a cytokine with known cytotoxic effects.
  • The precise mechanism of IL-1-induced cell death, particularly in combination with cycloheximide (CHX), requires elucidation.
  • Similarities between IL-1 and tumor necrosis factor (TNF) effects suggest a potential link.

Purpose of the Study:

  • To investigate the mechanism underlying IL-1-induced cytocidal effects in HeLa cells when combined with cycloheximide (CHX).
  • To determine if IL-1 cytotoxicity is a direct or indirect process.
  • To identify the specific molecular mediators involved in IL-1-induced cell death.

Main Methods:

  • HeLa cells were treated with Interleukin 1 (IL-1) and cycloheximide (CHX).
  • Supernatants were analyzed for cytotoxic activity on other cell lines.
  • Neutralizing antibodies against TNF were used to block cell death.
  • TNF levels were quantified using flow cytometry, fluorescence microscopy, and ELISA.
  • The role of TNF sheddase (TACE) was investigated using specific inhibitors.

Main Results:

  • IL-1/CHX treatment induced cell death patterns similar to TNF.
  • Supernatants from IL-1/CHX treated cells exhibited toxicity towards TNF-sensitive cells.
  • Neutralization of TNF abrogated IL-1/CHX-induced HeLa cell death.
  • Both soluble and transmembrane TNF were detected in treated HeLa cells.
  • Inhibition of TNF sheddase (TACE) enhanced both IL-1/CHX cytotoxicity and TNF levels.

Conclusions:

  • IL-1-induced cytotoxicity in HeLa cells with CHX is an indirect mechanism.
  • The process is dependent on the generation and function of both soluble and transmembrane TNF.
  • IL-1 treatment leads to an increased amount of transmembrane TNF, contributing to cell death.

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