Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation
Gaetane Woerly, Kohei Honda, Marc Loyens, Jean-Paul Papin, Johan Auwerx, Bart Staels, Monique Capron, David Dombrowicz, Gaetane Woerly, Kohei Honda, Marc Loyens, Jean-Paul Papin, Johan Auwerx, Bart Staels, Monique Capron, David Dombrowicz
Abstract
Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator-activated receptors (PPARs), PPAR-alpha and PPAR-gamma, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-alpha and -gamma are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-alpha and -gamma (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.
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References
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