The synthetic PPARgamma agonist troglitazone inhibits IL-5-induced CD69 upregulation and eosinophil-derived neurotoxin release from eosinophils.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates lipid metabolism. Recently, PPARgamma was reported to be a negative regulator in the immune system. Eosinophils also express PPARgamma, however, the role of PPARgamma in eosinophil functions is not well understood. Surface expression of CD69 and eosinophil-derived neurotoxin (EDN) release are well-known activation markers of eosinophils. We investigated the effect of a PPARgamma agonist on human eosinophil functions such as IL-5-induced CD69 surface expression and EDN release. IL-5 significantly induced eosinophil CD69 surface expression analyzed using flow cytometry and EDN release measured by ELISA. IL-5-induced eosinophil CD69 surface expression and EDN release were significantly inhibited by the synthetic PPARgamma agonist troglitazone, and these effects were reversed by a PPARgamma antagonist. The PPARgamma agonist troglitazone has a potent inhibitory effect on activation and degranulation of eosinophils, and it may be a therapeutic modality for the treatment of allergic diseases.
Matsuwaki
Yoshinori
Y
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Ueki
Shigeharu
S
Adachi
Tetsuya
T
Oyamada
Hajime
H
Kamada
Yumiko
Y
Yamaguchi
Kazutoshi
K
Kanda
Akira
A
Hamada
Kazuyuki
K
Kayaba
Hiroyuki
H
Chihara
Junichi
J
D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002478:Cells, Cultured; D002839:Chromans / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D047208:Eosinophil-Derived Neurotoxin / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D037181:Lectins, C-Type; D009943:Organophosphorus Compounds / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000494:pharmacology*; D000077288:Troglitazone; D015854:Up-Regulation / Q000187:drug effects; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002839:Chromans; D047208:Eosinophil-Derived Neurotoxin; D015848:Interleukin-5; D037181:Lectins, C-Type; D009943:Organophosphorus Compounds; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077288:Troglitazone; D000099192:CD69 Antigens; C051602:mifobate