Y-24180, an antagonist of platelet-activating factor, suppresses interleukin 5 production in cultured murine th(2)cells and human peripheral blood mononuclear cells.
Interleukin (IL)-5 has been shown to play an essential role in the pathogenesis of airway inflammation. We investigated the effect of 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6, 9-dimethyl-6 H -thieno[3,2- f ][1,2,4]triazolo[4,3- a][1,4]diazepine (Y-24180), an antagonist of platelet-activating factor (PAF), on the production of IL-5 in cultured D10.G4.1 cells, a murine Th(2)clone, and human peripheral blood mononuclear cells (PBMC). As a result, Y-24180 was found to suppress both the mRNA expression of IL-5 and the subsequent secretion of this cytokine in antigen-stimulated D10.G4.1 cells. Y-24180 also suppressed the production of IL-4, another Th(2)type cytokine, at the level of mRNA expression, however, it hardly affected the mRNA expression for IL-6 or IL-10, thus indicating it to have a selective action against IL-5 and IL-4. The suppressive effect of Y-24180 on the secretion of IL-5 by human PBMC was more potent than that of WEB2086, which is another PAF-antagonist. These results suggest that Y-24180 suppresses IL-5 production through a common pathway which also affects the production of IL-4, even though the mechanism remains to be elucidated as to whether the PAF-antagonistic actions are involved or not.
Kusuhara
H
H
Drug Discovery Laboratories, Welfide Corporation, Osaka, Japan. kusuhara@welfide.co.jp
Yamaguchi
S
S
Matsuyuki
H
H
Sugahara
K
K
Komatsu
H
H
Terasawa
M
M
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D015848:Interleukin-5; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine