IFN-γ/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: Novel finding of cycloheximide-regulating death receptor expression

  • Authors:
    • Fumiko Tanaka
    • Atsushi Kawakami
    • Mami Tamai
    • Hideki Nakamura
    • Nozomi Iwanaga
    • Yasumori Izumi
    • Kazuhiko Arima
    • Kouichiro Aratake
    • Mingguo Huang
    • Makoto Kamachi
    • Hiroaki Ida
    • Tomoki Origuchi
    • Katsumi Eguchi
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/ijmm.15.5.833
  • Pages: 833-839
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Abstract

The pathway of interferon γ (IFN-γ-induced suppression in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated endothelial cell apoptosis was investigated. rTRAIL triggered apoptosis of human umbilical vein endothelial cells (HUVECs) in a type II cell death manner. IFN-γ pretreatment significantly suppressed the expression of death receptor 4 (DR4) and DR5 on HUVECs, and inhibited apoptosis in response to TRAIL. IFN-γ rapidly phosphorylated signal transducers and activators of transcription 1 (STAT1) and STAT6 but did not enhance phosphorylation of STAT3, Akt and extracellular signal-regulated kinase (ERK) and nuclear translocation of NF-κB p65. Janus kinase (JAK)-induced phosphorylation of STAT1/6 appeared to be crucial since chemical inhibition of JAK abolished phosphorylation of STAT1/6, down-regulation of DR4/DR5 expression and IFN-γ-induced inhibition of TRAIL-mediated apoptosis. IFN-γ/JAK/STAT-induced suppression was regulated by cycloheximide (CHX)-sensitive mechanism since the use of CHX mimicked the action of chemical inhibition of JAK in regard to DR4/DR5 expression as well as TRAIL-mediated endothelial cell apoptosis. We have not yet clarified precise mechanism, however, the present data provide a novel finding that IFN-γ/JAK/STAT pathway elicits inhibition of TRAIL-mediated endothelial cell apoptosis through CHX-sensitive suppression of DR4/DR5.

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May 2005
Volume 15 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tanaka F, Kawakami A, Tamai M, Nakamura H, Iwanaga N, Izumi Y, Arima K, Aratake K, Huang M, Kamachi M, Kamachi M, et al: IFN-γ/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: Novel finding of cycloheximide-regulating death receptor expression. Int J Mol Med 15: 833-839, 2005
APA
Tanaka, F., Kawakami, A., Tamai, M., Nakamura, H., Iwanaga, N., Izumi, Y. ... Eguchi, K. (2005). IFN-γ/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: Novel finding of cycloheximide-regulating death receptor expression. International Journal of Molecular Medicine, 15, 833-839. https://doi.org/10.3892/ijmm.15.5.833
MLA
Tanaka, F., Kawakami, A., Tamai, M., Nakamura, H., Iwanaga, N., Izumi, Y., Arima, K., Aratake, K., Huang, M., Kamachi, M., Ida, H., Origuchi, T., Eguchi, K."IFN-γ/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: Novel finding of cycloheximide-regulating death receptor expression". International Journal of Molecular Medicine 15.5 (2005): 833-839.
Chicago
Tanaka, F., Kawakami, A., Tamai, M., Nakamura, H., Iwanaga, N., Izumi, Y., Arima, K., Aratake, K., Huang, M., Kamachi, M., Ida, H., Origuchi, T., Eguchi, K."IFN-γ/JAK/STAT pathway-induced inhibition of DR4 and DR5 expression on endothelial cells is cancelled by cycloheximide-sensitive mechanism: Novel finding of cycloheximide-regulating death receptor expression". International Journal of Molecular Medicine 15, no. 5 (2005): 833-839. https://doi.org/10.3892/ijmm.15.5.833