The synthetic PPARgamma agonist troglitazone inhibits eotaxin-enhanced eosinophil adhesion to ICAM-1-coated plates.
Accumulation and activation of eosinophils in tissue are critical events in the allergic inflammatory response and adhesion molecules play important roles in this process. We previously demonstrated that human eosinophils expressed a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), and that stimulation with a PPARgamma agonist attenuated cytokine/chemokine-induced eosinophil activation, such as survival, chemotaxis and degranulation. In the present study, we investigated the effect of troglitazone, a synthetic PPARgamma agonist, on adherence to intercellular adhesion molecule-1 (ICAM-1). Eosinophils were purified from human peripheral blood, and the functional adherence to recombinant soluble ICAM-1-coated plates was examined. We found that in the presence of eotaxin, troglitazone inhibited eosinophil adherence in a concentration-dependent manner. This novel activity appears to be associated with modulation of qualitative change of integrins in response to eotaxin, because quantitative reduction of CD11a, CD11b and CD18 expression by troglitazone was not observed using flow cytometry. The PPARgamma agonist troglitazone has a potent inhibitory effect on eosinophil adhesion to ICAM-1, and this may be a therapeutic modality for the treatment of eosinophil-related diseases including bronchial asthma.
Hirasawa
Hiroyuki
H
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Chiba
Takahito
T
Ueki
Shigeharu
S
Kamada
Yumiko
Y
Ito
Wataru
W
Takeda
Masahide
M
Fujita
Miyoshi
M
Kato
Hikari
H
Kayaba
Hiroyuki
H
Chihara
Junichi
J
D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D054413:Chemokine CCL11 / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D039481:CD11b Antigen; D018821:CD18 Antigens; D054413:Chemokine CCL11; D002839:Chromans; D047495:PPAR gamma; D010975:Platelet Aggregation Inhibitors; D045162:Thiazolidinediones; D018799:Intercellular Adhesion Molecule-1; D000077288:Troglitazone