Peroxisome proliferator-activated receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma.
Asthma is characterized by a predominant T(H)2 type immune response to airborne allergens. Controlling T(H)2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)gamma significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. A PPARgamma ligand, 15-deoxy-delta(12,14)-prostaglandin J(2), significantly inhibited production of the T(H)2 type cytokine IL-5 from T cells activated in vitro. More importantly, in a murine model of allergic asthma, mice treated orally with ciglitazone, a potent synthetic PPARgamma ligand, had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from these ciglitazone treated mice also produced less IFNgamma, IL-4, and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPARgamma may be effective treatments for asthmatic patients.
Mueller
Cynthia
C
Department of Veterinary Science, The Pennsylvania State University, University Park, PA 16802, USA.
Weaver
Veronika
V
Vanden Heuvel
John P
JP
August
Avery
A
Cantorna
Margherita T
MT
D000284:Administration, Oral; D000818:Animals; D000936:Antigen-Antibody Complex; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015848:Interleukin-5 / Q000096:biosynthesis; D008024:Ligands; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D012016:Reference Values; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014157:Transcription Factors / Q000276:immunology*; D016896:Treatment Outcome
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000936:Antigen-Antibody Complex; D016207:Cytokines; D015848:Interleukin-5; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D015230:Prostaglandin D2; C039671:ciglitazone