Abstract
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.
MeSH terms
-
Animals
-
Dendritic Cells / cytology
-
Dendritic Cells / drug effects
-
Dendritic Cells / immunology
-
Female
-
Humans
-
Immunosuppressive Agents / chemistry
-
Immunosuppressive Agents / isolation & purification
-
Immunosuppressive Agents / pharmacology*
-
Interleukin-12 / immunology
-
Interleukin-12 / metabolism
-
Interleukin-2 / immunology
-
Interleukin-2 / metabolism
-
Jurkat Cells
-
Lactams / isolation & purification
-
Lactams / pharmacology*
-
Lactones / chemistry
-
Lactones / isolation & purification
-
Lactones / pharmacology*
-
Lymphocyte Activation / drug effects
-
Lymphocyte Activation / immunology
-
Mice
-
Mice, Inbred C57BL
-
NF-kappa B / immunology
-
NF-kappa B / metabolism
-
Pseudomonas fluorescens / chemistry*
-
Pseudomonas fluorescens / metabolism
-
T-Lymphocytes / cytology
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / immunology
-
Transcription Factor AP-1 / immunology
-
Transcription Factor AP-1 / metabolism
Substances
-
FR 252921
-
Immunosuppressive Agents
-
Interleukin-2
-
Lactams
-
Lactones
-
NF-kappa B
-
Transcription Factor AP-1
-
Interleukin-12