Expression of PPARgamma in eosinophils and its functional role in survival and chemotaxis.
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.
Ueki
Shigeharu
S
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, 1-1-1, Hondo, Akita 010-8543, Japan.
Adachi
Tetsuya
T
Bourdeaux
Jessy
J
Oyamada
Hajime
H
Yamada
Yoshiyuki
Y
Hamada
Kazuyuki
K
Kanda
Akira
A
Kayaba
Hiroyuki
H
Chihara
Junichi
J
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
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