MicroRNA-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through modulating TRAF6

Pathog Dis. 2021 Apr 9;79(4):ftab018. doi: 10.1093/femspd/ftab018.

Abstract

Evidence indicates that macrophages play an important role in the immune system. Therefore, research involving inflammatory and oxidative stress responses in macrophages is of great significance. Many factors contribute to inflammation and oxidative stress, including Salmonella. We investigated the effect of the miR-139-5p/TRAF6 axis on the inflammatory and oxidative stress responses of Salmonella -infected macrophages. Our findings revealed that miR-139-5p decreased IL-1β and TNF-α levels to inhibit Salmonella-induced inflammatory responses in the RAW264.7 macrophage cell line. Furthermore, miR-139-5p inhibited Salmonella-induced oxidative stress by strengthening SOD, CAT and GSH-PX activity, as well as lowering the malondialdehyde level in the RAW264.7 macrophages cell line. Subsequently, it was verified that TRAF6 was a downstream target of miR-139-5p in RAW264.7 cells. Rescue assays indicated that the over-expression of miR-139-5p inhibits the effects of TRAF6 on inflammatory and oxidative stress responses including Salmonella infection in RAW264.7 cells. To our knowledge, this study is the first to verify that miR-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through regulating TRAF6. This discovery may offer new insights on inflammatory and oxidative stress responses in macrophages.

Keywords: TRAF6; inflammatory; macrophages; miR-139-5p; oxidative stress.

MeSH terms

  • Animals
  • Base Pairing
  • Base Sequence
  • Catalase / genetics
  • Catalase / metabolism
  • Gene Expression Regulation
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Host-Pathogen Interactions / genetics*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Malondialdehyde / metabolism
  • Mice
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Mimicry
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Oxidative Stress
  • RAW 264.7 Cells
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / metabolism
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • TNF Receptor-Associated Factor 6 / genetics*
  • TNF Receptor-Associated Factor 6 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • IL1B protein, mouse
  • Interleukin-1beta
  • Lipopolysaccharides
  • MIRN139 microRNA, mouse
  • MicroRNAs
  • Oligoribonucleotides
  • TNF Receptor-Associated Factor 6
  • TRAF6 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase