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Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages

  • Authors:
    • Song-Yun Deng
    • Le-Meng Zhang
    • Yu-Hang Ai
    • Pin-Hua Pan
    • Shuang-Ping Zhao
    • Xiao-Li Su
    • Dong-Dong Wu
    • Hong-Yi Tan
    • Li-Na Zhang
    • Allan Tsung
  • View Affiliations / Copyright

    Affiliations: Department of Intensive Care Unit, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1261-1269
    |
    Published online on: August 25, 2017
       https://doi.org/10.3892/ijmm.2017.3110
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Abstract

Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages.
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Copy and paste a formatted citation
Spandidos Publications style
Deng S, Zhang L, Ai Y, Pan P, Zhao S, Su X, Wu D, Tan H, Zhang L, Tsung A, Tsung A, et al: Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages. Int J Mol Med 40: 1261-1269, 2017.
APA
Deng, S., Zhang, L., Ai, Y., Pan, P., Zhao, S., Su, X. ... Tsung, A. (2017). Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages. International Journal of Molecular Medicine, 40, 1261-1269. https://doi.org/10.3892/ijmm.2017.3110
MLA
Deng, S., Zhang, L., Ai, Y., Pan, P., Zhao, S., Su, X., Wu, D., Tan, H., Zhang, L., Tsung, A."Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages". International Journal of Molecular Medicine 40.4 (2017): 1261-1269.
Chicago
Deng, S., Zhang, L., Ai, Y., Pan, P., Zhao, S., Su, X., Wu, D., Tan, H., Zhang, L., Tsung, A."Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages". International Journal of Molecular Medicine 40, no. 4 (2017): 1261-1269. https://doi.org/10.3892/ijmm.2017.3110
Copy and paste a formatted citation
x
Spandidos Publications style
Deng S, Zhang L, Ai Y, Pan P, Zhao S, Su X, Wu D, Tan H, Zhang L, Tsung A, Tsung A, et al: Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages. Int J Mol Med 40: 1261-1269, 2017.
APA
Deng, S., Zhang, L., Ai, Y., Pan, P., Zhao, S., Su, X. ... Tsung, A. (2017). Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages. International Journal of Molecular Medicine, 40, 1261-1269. https://doi.org/10.3892/ijmm.2017.3110
MLA
Deng, S., Zhang, L., Ai, Y., Pan, P., Zhao, S., Su, X., Wu, D., Tan, H., Zhang, L., Tsung, A."Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages". International Journal of Molecular Medicine 40.4 (2017): 1261-1269.
Chicago
Deng, S., Zhang, L., Ai, Y., Pan, P., Zhao, S., Su, X., Wu, D., Tan, H., Zhang, L., Tsung, A."Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages". International Journal of Molecular Medicine 40, no. 4 (2017): 1261-1269. https://doi.org/10.3892/ijmm.2017.3110
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