Signal transducer and activator of transcription-3 mediated neuroprotective effect of interleukin-6 on cobalt chloride mimetic hypoxic cell death in R28 cells

Mol Biol Rep. 2021 Aug;48(8):6197-6203. doi: 10.1007/s11033-021-06586-5. Epub 2021 Jul 27.

Abstract

Background: Hypoxic injury to retinal ganglionic cells and adjoining glia is implicated in glaucomatous optic neuropathy. The present study evaluates the effect of IL-6 on R28 retinal precursor cell line exposed to hypoxic injury.

Methods and results: Apoptotic cell death induced by hypoxia mimetic CoCl2 in R28 cells with or without IL-6 treatment was measured using cell viability assays and apoptotic markers. Oxidative stress was also measured. Hypoxia induced by mimetic CoCl2 led to a time and concentration dependent apoptosis of cells mediated by disruption of mitochondrial membrane potential and activation of caspase 3. Cells pre-treated with IL-6 demonstrated significantly higher viability and mitochondrial integrity under hypoxic conditions. A critical role of STAT3 was observed in mediating the cytoprotective effects of IL-6. Treatment of cells with IL-6 led to STAT3-mediated expression of the Bcl-2 family proteins and MnSOD.

Conclusions: The data from the present study indicate cytoprotective role of IL-6 and suggest a previously unreported mechanism of neuroprotection via STAT3 mediated signaling.

Keywords: Glaucoma; Hypoxia; IL-6; Neuroprotection; Retinal ganglion cells; STAT3.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Death / drug effects
  • Cell Hypoxia / physiology*
  • Cell Line
  • Cell Survival / drug effects
  • Cobalt / adverse effects
  • Cobalt / pharmacology
  • Hypoxia / physiopathology
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Rats
  • Retina / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects

Substances

  • Interleukin-6
  • Neuroprotective Agents
  • STAT3 Transcription Factor
  • Cobalt
  • cobaltous chloride