Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro
✍ Scribed by Cécile Besson Duvanel; Paul Honegger; Harrihar Pershadsingh; Douglas Feinstein; Jean-Marie Matthieu
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 219 KB
- Volume
- 71
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Peroxisome proliferator‐activated receptor gamma (PPAR‐γ) is a member of the nuclear hormone superfamily originally characterized as a regulator of adipocyte differentiation and lipid metabolism. In addition, PPAR‐γ has important immunomodulatory functions. If the effect of PPAR‐γ's activation in T‐cell‐mediated demyelination has been recently demonstrated, nothing is known about the role of PPAR‐γ in antibody‐induced demyelination in the absence of T‐cell interactions and monocyte/macrophage activation. Therefore, we investigated PPAR‐γ's involvement by using an in vitro model of inflammatory demyelination in three‐dimensional aggregating rat brain cell cultures. We found that PPAR‐γ 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‐γ agonist, partially protected aggregates from anti‐MOG demyelination. Heat shock responses and the expression of the proinflammatory cytokine tumor necrosis factor‐α 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‐γ agonists act not only on T cells but also on antibody‐mediated demyelination. This may represent a significant benefit in treating multiple sclerosis patients. © 2002 Wiley‐Liss, Inc.