Theophylline and dexamethasone induce peroxisome proliferator-activated receptor-gamma expression in human eosinophils.
Eosinophils are major effector cells in allergic diseases including asthma. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates immune reaction. We have previously demonstrated that human eosinophils express PPARgamma and that stimulation with a synthetic agonist for PPARgamma attenuated the factor-induced eosinophil survival and chemotaxis. However, the modulator of the eosinophil PPARgamma expression has not yet been studied. In this study, we investigated the effect of theophylline and dexamethasone (widely used drugs in the treatment of asthma) on PPARgamma expression in eosinophils. Purified human peripheral blood eosinophils were cultured, and therapeutic concentrations of theophylline and dexamethasone were added. Subsequently, PPARgamma was measured using quantitative real-time RT-PCR and flow cytometry. Theophylline and dexamethasone markedly enhanced both mRNA and protein levels of PPARgamma. These findings suggest that the increase in PPARgamma expression on eosinophils may play a role in the anti-inflammatory effects of theophylline and dexamethasone.
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Hondo, Akita, Japan.
Atsuko
A
Usami
Shigeharu
S
Ueki
Wataru
W
Ito
Yoshiki
Y
Kobayashi
Takahito
T
Chiba
Gulixian
G
Mahemuti
Hajime
H
Oyamada
Yumiko
Y
Kamada
Miyoshi
M
Fujita
Hikari
H
Kato
Norihiro
N
Saito
Hiroyuki
H
Kayaba
Junichi
J
Chihara
D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D003907:Dexamethasone; D013806:Theophylline