Interferon-γ rescues TNF-α-induced apoptosis mediated by up-regulation of TNFR2 on EoL-1 cells

• Published in: Experimental hematology Vol. 27; no. 3; pp. 512 - 519
• Main Authors: Horie, Takeo, Dobashi, Kunio, Iizuka, Kunihiko, Yoshii, Akihiro, Shimizu, Yasuo, Nakazawa, Tsugio, Mori, Masatomo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.1999
• Subjects: Antibodies, Monoclonal - pharmacology; Antigens, CD - biosynthesis; Antigens, CD - drug effects; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, CD - physiology; Apoptosis - drug effects; Apoptosis - physiology; Cell Differentiation - drug effects; EoL-1—Apoptosis—Tumor necrosis factor—Fas antigen; fas Receptor - immunology; fas Receptor - physiology; Humans; Interferon-gamma - pharmacology; Leukemia, Myeloid, Acute - pathology; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - physiology; Receptors, Tumor Necrosis Factor - biosynthesis; Receptors, Tumor Necrosis Factor - drug effects; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - physiology; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Recombinant Proteins; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation; EoL-1—Apoptosis—Tumor necrosis factor—Fas antigen
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(98)00058-7

Recent studies show that apoptosis is important for the resolution of chronic inflammation. Using a human myeloblastic leukemia cell line, EoL-1, we investigated the effect of interferon-γ (IFN-γ), which differentiates EoL-1 into monocyte/macrophage-like cells on Fas antigen (Fas)- and tumor necrosis factor-α (TNFα)-induced apoptosis. Both TNF and anti-Fas monoclonal antibody (CH-11) induced apoptosis of EoL-1 cells. Pretreatment with IFN-γ for 72 hours enhanced the CH-11-induced apoptosis with up-regulation of Fas. However, the treatment markedly inhibited the TNF-induced apoptosis. In flow cytometric analysis, EoL-1 expressed two types of tumor necrosis factor receptors (TNFR1 and TNFR2), and the expression of TNFR2 but not of TNFR1 was up-regulated significantly after the IFN-γ treatment. The TNF-induced apoptosis was mimicked by a TNFR1 stimulating antibody (htr-9), and was reversed by a TNFR1 blocking antibody (H398). Although the TNFR1-mediated cytotoxic signal was not affected by IFN-γ pretreatment, blocking TNFR2 by a specific antagonistic antibody (utr-1) canceled the inhibitory effect of IFN-γ. In conclusion, TNF-induced apoptosis was mediated preferentially by TNFR1, and the anti-apoptotic effect of IFN-γ was result from up-regulated TNFR2 in EoL-1 cell line. This cell line is a useful model to provide new insights into crosstalk among Fas/FasL-, TNF-, and IFN-γ-mediated signaling.