Cytocidal effect of interleukin 1 (IL-1) on HeLa cells is mediated by both soluble and transmembrane tumor necrosis factor (TNF).
Interleukin 1 (IL-1) is a pleiotropic cytokine able to induce cytocidal effect. The aim of the presented work was to analyze the mechanism of IL-1-induced cytocidal effect in HeLa cells in the presence of cycloheximide (CHX). We found that the pattern of IL-1-induced cell death shares significant similarities with the effect of tumor necrosis factor (TNF) in these cells. Subsequently, we identified IL-1 cytotoxicity as an indirect effect. The supernatant collected from the cells treated with IL-1 and CHX showed toxic activity towards IL-1-resistant while TNF-sensitive A9 cells. Furthermore, antibodies neutralizing TNF blocked HeLa cell death induced by IL-1/CHX. TNF was then detected in HeLa cells by means of flow cytometry, fluorescence microscopy and ELISA of detergent-soluble cell extracts. In the presence of an inhibitor of TNF sheddase (TACE), the cytotoxic effect of IL-1/CHX and the amount of TNF protein in detergent-soluble cell extracts were enhanced. These results suggest that in response to interleukin 1/CHX, the amount of transmembrane TNF is increased. Taken together, we demonstrated that the mechanism of IL-1 cytotoxic activity in HeLa cells in the presence of CHX depends on the function of soluble and transmembrane TNF.
Doszczak
Małgorzata
M
Cell Biology Unit, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-210 Gdańsk, Poland.
Pierzchalski
Arkadiusz
A
Cell Biology Unit, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-210 Gdańsk, Poland.
Grzenkowicz
Jolanta
J
Cell Biology Unit, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-210 Gdańsk, Poland.
Stasiłojć
Grzegorz
G
Cell Biology Unit, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-210 Gdańsk, Poland.
Bigda
Jacek J
JJ
Cell Biology Unit, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, ul. Dębinki 1, 80-210 Gdańsk, Poland. Electronic address: jjbigd@amg.gda.pl.
D000818:Animals; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D048069:Tumor Necrosis Factors / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D007375:Interleukin-1; D048069:Tumor Necrosis Factors