Nutrients, nuclear receptors, inflammation, immunity lipids, PPAR, and allergic asthma

The peroxisome proliferator-activated receptors (PPARs) belong to the larger superfamily of steroid/thyroid nuclear receptors. PPARγ is expressed in a number of hematopoietic cells, including dendritic cells, eosinophils, macrophages, and T cells. A number of lipids and synthetic compounds interact with PPARγ, that, depending on the cell type, results in the regulation of specific genes. There is now a large body of data indicating that allergic asthma is the result of a predominant type-2 helper T cell immune response including IL-4, -5 and -13, eosinophilic inflammation in the lungs, mucous production, and airway hyperresponsiveness (AHR). Targeting the production of these type-2 helper T cell mediated cytokines has been proposed as a way to regulate this disease. Because PPARγ ligands can affect T cell cytokine production in vitro, we have examined whether these ligands affect symptoms of allergic asthma in a murine model of this disease. We discuss data showing that ciglitazone and GW1929, two agonistic ligands for PPARγ, significantly inhibited airway inflammation during allergic asthma induction. Oral treatment with ciglitazone and GW1929 inhibited airway inflammation, with less of an effect on AHR. By contrast, intranasal exposure to GW1929 significantly reduced AHR following exposure to allergen, while GW9662, a PPARγ antagonist, had no effect. In vitro, T cells from ciglitazone-treated mice secreted significantly less IL-4 and IFN-γ in response to restimulation. These data suggest that PPARγ agonists may be useful for the treatment of allergic asthma.