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More MS news articles for January 2003

Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12503087&dopt=Abstract

J Neurosci Res 2003 Jan15;71(2):246-55
Duvanel CB, Honegger P, Pershadsingh H, Feinstein D, Matthieu JM.
Neurochemistry Laboratory, Department of Pediatrics, CHUV, Lausanne, Switzerland.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear hormone superfamily originally characterized as a regulator of adipocyte differentiation and lipid metabolism.

In addition, PPAR-gamma has important immunomodulatory functions.

If the effect of PPAR-gamma's activation in T-cell-mediated demyelination has been recently demonstrated, nothing is known about the role of PPAR-gamma in antibody-induced demyelination in the absence of T-cell interactions and monocyte/macrophage activation.

Therefore, we investigated PPAR-gamma's involvement by using an in vitro model of inflammatory demyelination in three-dimensional aggregating rat brain cell cultures.

We found that PPAR-gamma was not constitutively expressed in these cultures but was strongly up-regulated following demyelination mediated by antibodies directed against myelin oligodendrocyte glycoprotein (MOG) in the presence of complement.

Pioglitazone, a selective PPAR-gamma agonist, partially protected aggregates from anti-MOG demyelination.

Heat shock responses and the expression of the proinflammatory cytokine tumor necrosis factor-alpha were diminished by pioglitazone treatment.

Therefore, pioglitazone protection seems to be linked to an inhibition of glial cell proinflammatory activities following anti-MOG induced demyelination.

We show that PPAR-gamma agonists act not only on T cells but also on antibody-mediated demyelination.

This may represent a significant benefit in treating multiple sclerosis patients.