Differential effects of corticosteroids on the expression of cyclooxygenase-2, tumour necrosis factor-alpha and matrix metalloproteinase-9 in an animal model of migraine.
Nitric oxide (NO) directly activates trigeminal afferents innervating the dura mater and up-regulates inflammatory mediators. We evaluated NO-mediated up-regulation of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-9 (MMP-9), and the effect of glucocorticoid administration in an experimental animal model of migraine. COX-2 and TNF-alpha expression and MMP-9 activity were increased after continuous intravenous infusion of glyceryl trinitrate (GTN), a NO donor. Immunofluorescence staining demonstrated strong expression of these inflammatory mediators in the meningeal blood vessels. Methylprednisolone (MP) down-regulated MMP-9, which was reversed by RU486, a glucocorticoid receptor antagonist. COX-2 and TNF-alpha expression was not affected by MP or RU486 administration. These results suggest proinflammatory mediators are involved in the NO-mediated cascade of migraine pathogenesis. Further understanding of the activation of these inflammatory mediators at the transcriptional level may have therapeutic implications for future migraine treatments.
Kim
G-M
GM
Department of Neurology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea. kimgm@skku.edu
Jin
K-S
KS
Chung
C-S
CS
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects*; D008578:Meninges / Q000098:blood supply / Q000187:drug effects; D008775:Methylprednisolone / Q000494:pharmacology*; D008881:Migraine Disorders / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects*
D005938:Glucocorticoids; D020030:Nitric Oxide Donors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; D005996:Nitroglycerin; D008775:Methylprednisolone