FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action.
A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibited splenic proliferation stimulated with LPS, insensitive to calcinuerin inhibitor. In this study, FR252921 was found to inhibit IL-2 and IL-12 production as well as proliferaion of splenocyte. Analysis of transcription activity revealed that FR252921 inhibited activating protein-1 (AP-1). Exposures of antigen presenting cells (APC) to FR252921 attenuated proliferation supplemented by naïve T cells. Further, FR252921 strongly suppressed splenic dendritic cell proliferation stimulated with LPS and anti-CD40 mAb, while it did not inhibit purified T cell activation, including CD154 expression and IL-2 production. These results suggest that APC is dominant target cell population.
Fujine
Kiyotaka
K
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. kiyotaga-fujine@po.fujisawa.co.jp
Abe
Fumie
F
Seki
Nobuo
N
Ueda
Hirotsugu
H
Hino
Motohiro
M
Fujii
Takashi
T
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D007769:Lactams / Q000302:isolation & purification / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011551:Pseudomonas fluorescens / Q000737:chemistry* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism
C474178:FR 252921; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007769:Lactams; D007783:Lactones; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D018664:Interleukin-12