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PPARalpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-kappaB and

Sriram Ramanan1, Mitra Kooshki, Weiling Zhao

  • 1Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Free Radical Biology & Medicine
|October 15, 2008
PubMed

Insights

Whole-brain irradiation triggers microglial activation and inflammation, leading to cognitive deficits. Peroxisomal proliferator-activated receptor (PPAR)alpha agonists can reduce this radiation-induced microglial inflammation, potentially protecting against cognitive impairment.

Area of Science:

  • Neuroscience
  • Radiology
  • Immunology

Background:

  • Whole-brain irradiation (WBI) causes long-term cognitive impairment.
  • Irradiation increases activated microglia, leading to chronic inflammation and reduced neurogenesis.
  • Targeting microglial activation is crucial for mitigating WBI side effects.

Purpose of the Study:

  • To investigate if peroxisomal proliferator-activated receptor (PPAR)alpha agonists can reduce radiation-induced microglial inflammation.
  • To examine the effects of PPARalpha agonists on inflammatory markers and transcription factors in irradiated microglial cells.

Main Methods:

  • Murine microglial BV-2 cells were irradiated with gamma-rays (2-10 Gy).
  • Gene expression (IL-1beta, TNFalpha), protein levels (Cox-2), ROS generation, and transcription factor activity (AP-1, NF-kappaB) were measured.
  • Cells were pretreated with PPARalpha agonists (GW7647, Fenofibrate) before irradiation.

Main Results:

  • Irradiation increased IL-1beta, TNFalpha, Cox-2, ROS, and AP-1/NF-kappaB DNA-binding activity.
  • PPARalpha agonist pretreatment significantly inhibited these radiation-induced inflammatory responses.
  • Inhibition involved decreased NF-kappaB p65 nuclear translocation and c-jun phosphorylation.

Conclusions:

  • PPARalpha activation effectively modulates the microglial inflammatory response to radiation.
  • PPARalpha agonists show potential for preventing WBI-induced cognitive impairment by reducing neuroinflammation.

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