title: Expression of PPARgamma in eosinophils and its functional role in survival and chemotaxis.
abstract: Eosinophils play a pivotal role in the mechanism of allergic diseases including asthma. Interleukin-5 (IL-5) and eotaxin are critical cytokines/chemokines for eosinophil activation. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates lipid metabolism. Recent evidence has suggested that PPARgamma serves as a negative regulator in the immune system. In the present study, we investigated the expression of PPARgamma and effect of PPARgamma agonist on human eosinophils. We demonstrated that purified eosinophils and Eol-1 cells express PPARgamma at the mRNA and protein levels. The PPARgamma agonist troglitazone reduced the IL-5-stimulated, but not spontaneous, eosinophil survival in a concentration-dependent manner. Moreover, the eotaxin-directed eosinophil chemotaxis was dose-dependently inhibited by troglitazone. Our results suggest that the administration of the PPARgamma agonists thiazolidinediones could be a new therapeutic modality for the treatment of allergic diseases such as asthma.
authors.affiliation: Department of Clinical and Laboratory Medicine, Akita University School of Medicine, 1-1-1, Hondo, Akita 010-8543, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.forename: Jessy
authors.initials: J
authors.lastname: Bourdeaux
authors.forename: Hajime
authors.initials: H
authors.lastname: Oyamada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hamada
authors.forename: Akira
authors.initials: A
authors.lastname: Kanda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kayaba
authors.forename: Junichi
authors.initials: J
authors.lastname: Chihara
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism* / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism* / Q000502:physiology*; D000077288:Troglitazone
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002839:Chromans; D015848:Interleukin-5; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone