Salmonella‑induced miR‑155 enhances necroptotic death in macrophage cells via targeting RIP1/3

Young-Tae Ro1, Guk-Heui Jo2, Sun-Ah Jung2

  • 1Laboratory of Biochemistry, Graduate School of Medicine, Konkuk University, Chungju, Chungcheong 27478, Republic of Korea.

Insights

Salmonella infection increases microRNA-155, leading to macrophage cell death via RIP1/3-induced necroptosis and PARP-1-mediated necrosis. Inhibiting RIP1 enhances cell survival, revealing distinct programmed cell death pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Salmonella Typhimurium is a pathogen that causes host-cell death.
  • MicroRNAs (miRNAs) play crucial roles in regulating cellular processes, including cell death.
  • Understanding the mechanisms of Salmonella-induced cell death is vital for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the role of microRNA-155 (miR-155) in Salmonella-induced macrophage cell death.
  • To elucidate the molecular pathways involved in miR-155-mediated cell death, focusing on receptor-interacting protein (RIP) kinases and poly (ADP-ribose) polymerase-1 (PARP-1).

Main Methods:

  • Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure miR-155 expression.
  • Western blot analysis to detect RIP1 and RIP3 protein levels.
  • Cell viability assays and assessment of poly (ADP-ribose) polymerase-1 (PARP-1) cleavage.

Main Results:

  • Salmonella infection significantly upregulated miR-155 expression in RAW 264.7 macrophages.
  • miR-155 upregulation enhanced macrophage cell death and increased RIP1 and RIP3 levels.
  • Inhibition of RIP1 using necrostatin-1 improved the viability of infected and miR-155-transfected macrophages.
  • miR-155 induction promoted PARP-1 cleavage, indicating enhanced necrosis.

Conclusions:

  • miR-155 plays a key role in Salmonella-induced macrophage death.
  • RIP1/3-induced necroptosis and PARP-1-mediated necrosis are distinct pathways contributing to programmed cell death in Salmonella-infected macrophages.
  • Targeting miR-155 or its downstream effectors may offer therapeutic potential against Salmonella infections.

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