Methionine enkephalin inhibits influenza A virus infection through upregulating antiviral state in RAW264.7 cells

Int Immunopharmacol. 2020 Jan:78:106032. doi: 10.1016/j.intimp.2019.106032. Epub 2019 Dec 10.

Abstract

MENK, as an immune adjuvant, has potential immune-regulatory activity on innate and adaptive immune cells. The aim of this work was to investigate the antiviral effect of MENK on influenza virus-infected murine macrophage cells (RAW264.7) and its underlying mechanisms. The results showed that MENK markedly inhibited influenza A virus (H1N1) replication in pre- and post-MENK treatment, especially in pre-MENK treatment. The mechanisms exploration revealed that MENK (10 mg/mL) significantly inhibited the nucleoprotein (NP) of influenza virus and up-regulated levels of IL-6, TNF-α and IFN-β compared with those in H1N1 control group. Further experiments confirmed that antiviral effects of MENK was associated with promotion of opioid receptor (MOR) as well as activation of NF-κB p65 inducing cellular antiviral status. The data suggest that MENK should be potential candidate for prophylactic or therapeutic treatment against H1N1 influenza virus.

Keywords: Antiviral effect; Influenza A virus; Methionine enkephalin; Opioid receptor; RAW264.7 cell; Toll-like receptors.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Enkephalin, Methionine / pharmacology*
  • Enkephalin, Methionine / therapeutic use
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza, Human / drug therapy*
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Interferon-beta / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • RAW 264.7 Cells
  • Receptors, Opioid, mu / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects
  • Virus Replication / drug effects
  • Virus Replication / immunology

Substances

  • Adjuvants, Immunologic
  • Interleukin-6
  • Oprm protein, mouse
  • Receptors, Opioid, mu
  • Rela protein, mouse
  • Tnf protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Enkephalin, Methionine
  • Interferon-beta