Open Access

Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB

  • Authors:
    • Shuang Wu
    • Tatsuo Kanda
    • Shingo Nakamoto
    • Xia Jiang
    • Masato Nakamura
    • Reina Sasaki
    • Yuki Haga
    • Hiroshi Shirasawa
    • Osamu Yokosuka
  • View Affiliations

  • Published online on: June 16, 2016     https://doi.org/10.3892/ijmm.2016.2643
  • Pages: 475-481
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β are often observed in the sera of hepatitis B virus (HBV)-infected patients. It is well known that these cytokines activate nuclear factor-κB (NF-κB)-signaling, and are associated with endoplasmic reticulum (ER) stress. We investigated whether HBV or HBV X protein (HBx) enhanced the activation of NF-κB in the presence of TNF and/or IL-1β, and their effects on the expression of metabolic pathway‑associated genes. We examined whether HBV or HBx enhanced cytokine-induced activation of NF-κB in hepatocytes, using a reporter assay, in the presence or absence of TNF and/or IL-1β. The expression of insulin-like growth factor binding protein 1 (IGFBP1), one of the NF-κB target genes was also examined. The expression of metabolic pathway-associated genes in HepG2 and HepG2.2.15 cells in the presence or absence of TNF was evaluated by RT-qPCR. Human hepatocytes expressed TNF receptors and IL-1 receptors. NF-κB was activated by cooperation between HBx and TNF in human hepatocytes. We observed IGFBP1 expression in HBV infection and that a number of metabolic pathway-associated genes were upregulated in HepG2.2.15 cells, compared with HepG2 cells with or without TNF treatment. We observed the cooperative effects of HBV and TNF which enhanced the activation of NF-κB as well as upregulated the expression of metabolic pathway-associated genes in hepatocytes. These effects may be important in the development of HBV-associated metabolic syndrome.
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August-2016
Volume 38 Issue 2

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

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Spandidos Publications style
Wu S, Kanda T, Nakamoto S, Jiang X, Nakamura M, Sasaki R, Haga Y, Shirasawa H and Yokosuka O: Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB. Int J Mol Med 38: 475-481, 2016
APA
Wu, S., Kanda, T., Nakamoto, S., Jiang, X., Nakamura, M., Sasaki, R. ... Yokosuka, O. (2016). Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB. International Journal of Molecular Medicine, 38, 475-481. https://doi.org/10.3892/ijmm.2016.2643
MLA
Wu, S., Kanda, T., Nakamoto, S., Jiang, X., Nakamura, M., Sasaki, R., Haga, Y., Shirasawa, H., Yokosuka, O."Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB". International Journal of Molecular Medicine 38.2 (2016): 475-481.
Chicago
Wu, S., Kanda, T., Nakamoto, S., Jiang, X., Nakamura, M., Sasaki, R., Haga, Y., Shirasawa, H., Yokosuka, O."Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB". International Journal of Molecular Medicine 38, no. 2 (2016): 475-481. https://doi.org/10.3892/ijmm.2016.2643