title: Is the Wnt/β-catenin pathway involved in the anti-inflammatory activity of glucocorticoids in spinal cord injury?
abstract: The Wnt canonical or the Wnt/β-catenin pathway has been implicated in the regulation of several physiopathological pathways such as inflammation. Glucocorticoids (GCs) are administered widely to treat inflammation in several diseases, including spinal cord injury (SCI). The aim of this study was to evaluate whether the Wnt canonical pathway is involved in experimental SCI and whether it is implicated in the anti-inflammatory activity of two different GCs: the methylprednisolone sodium succinate (MPSS), considered the standard treatment for acute SCI, and mometasone furoate (MF), mainly administered for the treatment of airway and skin diseases. Experimental SCI was induced in mice by surgical spinal cord compression at the T6-T7 level. Then, mice were treated with MPSS (6 mg/kg) or MF (0.1 mg/kg) for 7 days until they were killed. Both GCs were found to modulate the Wnt canonical pathway, but in particular, the MF treatment was shown to restore completely the downregulated pathway in SCI. The MF treatment also significantly increased peroxisome proliferator-activated receptor-γ, a Wnt target gene with anti-inflammatory properties, compared with MPSS, and it also inhibited the levels of the proinflammatory cytokines interleukin 1β and tumor necrosis factor-α. Here, we suggest that MF has more efficacy than MPSS in inhibiting inflammation in an SCI experimental model and we propose the β-catenin/peroxisome proliferator-activated receptor-γ axis as the mechanism by which MF exerts these beneficial effects.
authors: IRCCS Centro Neurolesi 'Bonino-Pulejo', Contrada Casazza, Messina, Italy.
authors: Rosaliana
authors: R
authors: Libro
authors: Sabrina
authors: S
authors: Giacoppo
authors: Placido
authors: P
authors: Bramanti
authors: Emanuela
authors: E
authors: Mazzon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D051177:Catenins / Q000378:metabolism; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000627:therapeutic use; D051379:Mice; D000068656:Mometasone Furoate / Q000627:therapeutic use; D009187:Myelitis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D051177:Catenins; D005938:Glucocorticoids; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000068656:Mometasone Furoate; D008776:Methylprednisolone Hemisuccinate