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Delta-opioid receptors attenuate TNF-α-induced MMP-2 secretion from human ONH astrocytes

Naseem Akhter1, Melissa Nix, Yasir Abdul

  • 1Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina.

Investigative Ophthalmology & Visual Science
|September 14, 2013
PubMed
Abstract

Insights

The delta-opioid receptor agonist SNC-121 reduces tumor necrosis factor-alpha (TNF-α)-induced matrix metalloproteinase-2 (MMP-2) secretion in optic nerve head astrocytes. This effect involves the p38 MAP kinase and NF-κB signaling pathways.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Cell Biology

Background:

  • Tumor necrosis factor-alpha (TNF-α) can induce matrix metalloproteinase-2 (MMP-2) secretion.
  • MMP-2 plays a role in optic nerve head (ONH) remodeling and disease.
  • Understanding the regulation of MMP-2 secretion is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the signaling mechanisms by which the delta-opioid receptor agonist SNC-121 attenuates TNF-α-induced MMP-2 secretion from human ONH astrocytes.
  • To determine the involvement of p38 mitogen-activated protein (MAP) kinase and nuclear factor-kappa B (NF-κB) signaling pathways in this process.

Main Methods:

  • Human ONH astrocytes were treated with SNC-121 and/or TNF-α.
  • Inhibitors of p38 MAP kinase (SB-203580) and NF-κB (Helenalin) were used to block signaling pathways.
  • Western blotting was employed to measure protein phosphorylation and expression.
  • Immunocytochemistry was used to assess NF-κB translocation.

Main Results:

  • SNC-121 significantly reduced TNF-α-induced MMP-2 secretion from ONH astrocytes.
  • The inhibitory effect of SNC-121 was blocked by the delta-opioid receptor antagonist naltrindole.
  • TNF-α treatment increased p38 MAP kinase phosphorylation and NF-κB expression, which were attenuated by SNC-121.
  • Inhibitors of p38 MAP kinase and NF-κB blocked TNF-α-induced MMP-2 secretion.

Conclusions:

  • SNC-121 effectively attenuates TNF-α-induced MMP-2 secretion in human ONH astrocytes.
  • The p38 MAP kinase and NF-κB signaling pathways are critical mediators of TNF-α-induced MMP-2 secretion.
  • SNC-121 exerts its inhibitory effects through negative regulation of both p38 MAP kinase and NF-κB signaling.
Keywords:
astrocytesglaucomamatrix metalloproteinasesopioidsoptic nerve head

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