Is the Wnt/β-catenin pathway involved in the anti-inflammatory activity of glucocorticoids in spinal cord injury?

Rosaliana Libro, Sabrina Giacoppo, Placido Bramanti, Emanuela Mazzon

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalNeuroReport
DOIs
Publication statusAccepted/In press - Aug 10 2016

Fingerprint

Mometasone Furoate
Catenins
Wnt Signaling Pathway
Methylprednisolone Hemisuccinate
Spinal Cord Injuries
Glucocorticoids
Anti-Inflammatory Agents
Peroxisome Proliferator-Activated Receptors
Inflammation
Spinal Cord Compression
Interleukin-1
Skin Diseases
Theoretical Models
Down-Regulation
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Is the Wnt/β-catenin pathway involved in the anti-inflammatory activity of glucocorticoids in spinal cord injury? / Libro, Rosaliana; Giacoppo, Sabrina; Bramanti, Placido; Mazzon, Emanuela.

In: NeuroReport, 10.08.2016.

Research output: Contribution to journalArticle

@article{82fed9f9843145d79f41f2315d814ea9,
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.",
author = "Rosaliana Libro and Sabrina Giacoppo and Placido Bramanti and Emanuela Mazzon",
year = "2016",
month = "8",
day = "10",
doi = "10.1097/WNR.0000000000000663",
language = "English",
journal = "NeuroReport",
issn = "0959-4965",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Is the Wnt/β-catenin pathway involved in the anti-inflammatory activity of glucocorticoids in spinal cord injury?

AU - Libro, Rosaliana

AU - Giacoppo, Sabrina

AU - Bramanti, Placido

AU - Mazzon, Emanuela

PY - 2016/8/10

Y1 - 2016/8/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84981484245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981484245&partnerID=8YFLogxK

U2 - 10.1097/WNR.0000000000000663

DO - 10.1097/WNR.0000000000000663

M3 - Article

AN - SCOPUS:84981484245

JO - NeuroReport

JF - NeuroReport

SN - 0959-4965

ER -