The synthetic PPARgamma agonist troglitazone inhibits IL-5-induced CD69 upregulation and eosinophil-derived neurotoxin release from eosinophils.

Yoshinori Matsuwaki, Shigeharu Ueki, Tetsuya Adachi, Hajime Oyamada, Yumiko Kamada, Kazutoshi Yamaguchi, Akira Kanda, Kazuyuki Hamada, Hiroyuki Kayaba, Junichi Chihara

Index: Pharmacology 74(4) , 169-73, (2005)

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Abstract

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.