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. PPARgamma 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 PPARgamma, 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 PPARgamma 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 PPARgamma, 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 PPARgamma antagonist, had no effect. In vitro, T cells from ciglitazone-treated mice secreted significantly less IL-4 and IFN-gamma in response to restimulation. These data suggest that PPARgamma agonists may be useful for the treatment of allergic asthma.
August
Avery
A
Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, 16802, USA.
Mueller
Cynthia
C
Weaver
Veronika
V
Polanco
Tiffany A
TA
Walsh
Elizabeth R
ER
Cantorna
Margherita T
MT
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006967:Hypersensitivity; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008055:Lipids / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D008055:Lipids; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D007073:Immunoglobulin E