Interferon-gamma Induces Ice Gene Expression and Enhances Cellular Susceptibility to Apoptosis in the U937 Leukemia Cell Line

Authors: Tamura T.¹; Ueda S.¹; Yoshida M.¹; Matsuzaki M.²; Mohri H.¹; Okubo T.¹

Source: Biochemical and Biophysical Research Communications, Volume 229, Number 1, December 1996 , pp. 21-26(6)

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Abstract:

The roles of interferons (IFNs) in apoptosis are not fully understood. In this study we show that in the U937 monoblastic leukemia cell line, pretreatment with IFN-gamma enhanced sensitivity to apoptosis triggered by gamma-irradiation or antitumor agents (etoposide or adriamycin), as well as by anti-Fas antibody. In addition, IFN-gamma caused an increased expression of the interleukin-1beta-converting enzyme ( Ice ) gene, following strong induction of the interferon regulatory factor-1 ( IRF-1 ) gene, the product of which is a transcriptional activator of the Ice gene. An inhibitor of ICE/Ced-3 family proteases, Z-Asp-CH 2 -DCB, blocked apoptosis in control cells as well as in IFN-gamma-pretreated cells. These results suggest that enhanced susceptibility of IFN-gamma-pretreated cells to apoptosis is mediated through the induction of Ice by IRF-1. This pathway is not affected by interleukin-1beta (IL-1beta) since neutralizing antibody against IL-1beta failed to suppress the IFN-gamma-mediated enhancement of cell death, and IL-1beta itself did not mimic the effect of IFN-gamma.

Language: English

Document Type: Research article

Affiliations: 1: The First Department of Internal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Yokohama, 236, Japan 2: Division of Blood Transfusion, Yokohama City University School of Medicine, 3-9 Fukuura, Yokohama, 236, Japan

Publication date: 1996-12-01