title: Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis.
abstract: Peroxisome Proliferator-Activated Receptors (PPAR) are transcription factors suggested to be involved in inflammatory lesions of autoimmune encephalomyelitis and multiple sclerosis (MS). Our objective was to assess whether Natalizumab (NTZ) therapy is associated with alterations of PPAR expression in MS patients. We analyzed gene expression of PPAR in peripheral blood mononuclear cells (PBMC) as well as blood inflammatory markers in women with MS previously medicated with first-line immunomodulators (baseline) and after NTZ therapy. No differences in PPARα, PPARβ/δ, PPARγ, and CD36 mRNA expression were found in PBMC between patients under baseline and healthy controls. At three months, NTZ increased PPARβ/δmRNA (p= 0.009) in comparison to baseline, while mRNA expression of PPARγand CD36 (a well-known PPAR target gene) was lower in comparison to healthy controls (p= 0.026 andp= 0.028, resp.). Although these trends of alterations remain after six months of therapy, the results were not statistically significant. Osteopontin levels were elevated in patients (p= 0.002) and did not change during the follow-up period of NTZ treatment. These results suggest that PPAR-mediated processes may contribute to the mechanisms of action of NTZ therapy.
authors.affiliation: Interdisciplinary Centre of Research Egas Moniz (CiiEM), Caparica, Portugal.
authors.forename: Véronique
authors.initials: V
authors.lastname: Ferret-Sena
authors.affiliation: Interdisciplinary Centre of Research Egas Moniz (CiiEM), Caparica, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maia E Silva
authors.affiliation: Interdisciplinary Centre of Research Egas Moniz (CiiEM), Caparica, Portugal; Neurology Service, Hospital dos Capuchos, Centro Hospitalar Lisboa Central, Lisboa, Portugal.
authors.forename: Armando
authors.identifier: 0000-0002-5021-5769
authors.initials: A
authors.lastname: Sena
authors.affiliation: Interdisciplinary Centre of Research Egas Moniz (CiiEM), Caparica, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Cavaleiro
authors.affiliation: Department of Neurology, Hospital Beatriz Angelo, Loures, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Vale
authors.affiliation: University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Derudas
authors.affiliation: University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France; University of Côte d'Azur, CHU, CNRS, Inserm, IRCAN, Nice, France.
authors.forename: Giulia
authors.identifier: 0000-0001-8048-8138
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
authors.affiliation: University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Bart
authors.identifier: 0000-0002-3784-1503
authors.initials: B
authors.lastname: Staels