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Activation of NF-κB by alloferon through down-regulation of antioxidant proteins and IκBα

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A Correction to this article was published on 19 October 2022

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Abstract

Alloferon is a 13-amino acid peptide isolated from the bacteria-challenged larvae of the blow fly Calliphora vicina. The pharmaceutical value of the peptide has been well demonstrated by its capacity to stimulate NK cytotoxic activity and interferon (IFN) synthesis in animal and human models, as well as to enhance antiviral and antitumor activities in mice. Antiviral and the immunomodulatory effectiveness of alloferon have also been supported clinically proved in patients suffering with herpes simplex virus (HSV) and human papilloma virus (HPV) infections. To elucidate molecular response to alloferon treatment, we initially screened a model cell line in which alloferon enhanced IFN synthesis upon viral infection. Among the cell lines tested, Namalva was chosen for further proteomic analysis. Fluorescence difference gel electrophoresis (DIGE) revealed that the levels of a series of antioxidant proteins decreased after alloferon treatment, while at least three glycolytic enzymes and four heat-shock proteins were increased in their expression levels. Based on the result of our proteomic analysis, we speculated that alloferon may activate the NF-κB signaling pathway. IκB kinase (IKK) assay, Western blot analysis on IκBα and its phosphorylated form at Ser 32, and an NF-κB reporter assay verified our proteomics-driven hypothesis. Thus, our results suggest that alloferon potentiates immune cells by activating the NF-κB signaling pathway through regulation of redox potential. Since NF-κB activation is involved in IFN synthesis, our results provide further clues as to how the alloferon peptide may stimulate IFN synthesis.

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Abbreviations

DIGE:

Fluorescence difference gel electrophoresis

GSTP1:

Glutathione S-transferase P

HPV:

Human papilloma virus

HSV:

Herpes simplex virus

IDPc:

NADP+-dependent isocitrate dehydrogenase

IFN:

Interferon

LC-ESI-MS/MS:

Liquid chromatography-electrospray ionization-tandem mass spectrometry

MALDI-MS/MS:

Matrix-assisted laser desorption ionization tandem mass spectrometry

PDIA3:

Protein disulfide-isomerase A3

PI3K:

Phosphatidylinositol-4, 5-bisphosphate 3-kinase

PRX4:

Peroxiredoxin 4

ROS:

Reactive oxygen species

TLR:

Toll-like receptor

TR1:

Thioredoxin reductase 1

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Acknowledgements

We thank Profs. Wang-Jae Lee and Jae Seung Kang (Seoul National University College of Medicine, Seoul, Korea) for their critical review of the manuscript. This study was financially supported by the Korea-Russia Scientific and Technological Cooperation Center, affiliated at Korea Institute of Science and Technology.

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Authors and Affiliations

  1. Life Sciences Division, Korea Institute of Science and Technology, 39-1 Hawolgok, Seongbuk, Seoul, 136-791, Korea

    Myung-Jeom Ryu, Seok-Ho Hong, Hyesung Jeon & Cheolju Lee

  2. Functional Proteomics Center, Korea Institute of Science and Technology, 39-1 Hawolgok, Seongbuk, Seoul, 136-791, Korea

    Myung-Jeom Ryu & Myeong-Hee Yu

  3. Laboratory of Insect Biopharmacology and Immunology, Biological Research Institute, St. Petersburg University, 2 Oranienbaumskoye shosse, St. Petersburg, 199504, Russia

    Vadim Anikin & Sergey Chernysh

  4. Laboratory of Antiviral Medicines and Interferon Inducers, Institute of Influenza, Professor Popov Street, 15/17, St. Petersburg, 197022, Russia

    Vadim Anikin

  5. Department of Chemistry, Kookmin University, 861-1 Jeongneung, Seongbuk, Seoul, 136-702, Korea

    Yeon Gyu Yu

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  1. Myung-Jeom Ryu
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  2. Vadim Anikin
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  7. Sergey Chernysh
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Correspondence to Cheolju Lee.

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Ryu, MJ., Anikin, V., Hong, SH. et al. Activation of NF-κB by alloferon through down-regulation of antioxidant proteins and IκBα. Mol Cell Biochem 313, 91–102 (2008). https://doi.org/10.1007/s11010-008-9746-0

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  • DOI: https://doi.org/10.1007/s11010-008-9746-0

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