TY - JOUR
T1 - Peroxisome proliferator-activated receptor γ ligands attenuate immunological symptoms of experimental allergic asthma
AU - Mueller, Cynthia
AU - Weaver, Veronika
AU - Vanden Heuvel, John P.
AU - August, Avery
AU - Cantorna, Margherita T.
N1 - Funding Information:
The authors thank Ben Belda and Dan Hannon as well as Dr. Craig A. Paul of the Penn State DNA Microarray Facility for their contributions. Oligonucleotides for the production of the gene expression microarrays were obtained in part as the result of the College of Agricultural Sciences seed grant program (J.V.H.) and a consortium of users in the Department of Veterinary Science and Department of Nutrition, Penn State University. Supported in part by AI51626 (to A.A.) and NIH-NINDS 1R01 NS38888-01A2 (to M.T.C.) from the NIH.
PY - 2003/10/15
Y1 - 2003/10/15
N2 - Asthma is characterized by a predominant TH2 type immune response to airborne allergens. Controlling TH2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)γ significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. A PPARγ ligand, 15-deoxy-delta(12,14) -prostaglandin J(2), significantly inhibited production of the TH2 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 PPARγ ligand, had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from these ciglitazone treated mice also produced less IFNγ, IL-4, and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPARγ may be effective treatments for asthmatic patients.
AB - Asthma is characterized by a predominant TH2 type immune response to airborne allergens. Controlling TH2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)γ significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. A PPARγ ligand, 15-deoxy-delta(12,14) -prostaglandin J(2), significantly inhibited production of the TH2 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 PPARγ ligand, had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from these ciglitazone treated mice also produced less IFNγ, IL-4, and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPARγ may be effective treatments for asthmatic patients.
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U2 - 10.1016/j.abb.2003.08.006
DO - 10.1016/j.abb.2003.08.006
M3 - Article
C2 - 14522590
AN - SCOPUS:0141540467
SN - 0003-9861
VL - 418
SP - 186
EP - 196
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -