PPAR-α Modulates the Anti-Inflammatory Effect of Melatonin in the Secondary Events of Spinal Cord Injury.
Melatonin is the principal secretory product of the pineal gland, and its role as an immunomodulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and reduces the development of inflammation and tissue injury events associated with spinal cord trauma. Previous results suggest that peroxisome proliferator-activated receptor α (PPAR-α), a nuclear receptor protein that functions as a transcription factor activated by fatty acids, plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI).With the aim to characterize the role of PPAR-α in melatonin-mediated anti-inflammatory activity, we tested the efficacy of melatonin (30 mg/kg) in an experimental model of spinal cord trauma, induced in mice, by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-α KO) with wild-type (WT) mice.The results obtained indicate that melatonin-mediated anti-inflammatory activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, melatonin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, pro-inflammatory cytokine expression, nuclear factor κB (NF-κB) activation, and inducible nitric oxide synthase (iNOS) expression. This study indicates that PPAR-α can contribute to the anti-inflammatory activity of melatonin in SCI.
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
I
I
Paterniti
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
M
M
Campolo
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
M
M
Cordaro
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
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D
Impellizzeri
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
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R
Siracusa
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
R
R
Crupi
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy.
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E
Esposito
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. salvator@unime.it.|Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, MO, 63103, USA. salvator@unime.it.
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http://orcid.org/0000-0001-6131-3690
S
Cuzzocrea
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy*; D008550:Melatonin / Q000494:pharmacology*; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin
Melatonin; Myeloperoxidase; NF-κB; PPAR-α; iNOS
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