Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation.
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.
Woerly
Gaetane
G
Institut National de la Santé et de la Recherche Médicale (INSERM), U547-IFR17, Institut Pasteur de Lille, France.
Honda
Kohei
K
Loyens
Marc
M
Papin
Jean-Paul
JP
Auwerx
Johan
J
Staels
Bart
B
Capron
Monique
M
Dombrowicz
David
D
D000813:Anilides / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002633:Chemotaxis / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D050990:GATA3 Transcription Factor; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000378:metabolism; D045162:Thiazolidinediones; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D000077154:Rosiglitazone; C039671:ciglitazone