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 naive T cells. Further, FR252921 strongly suppressed splenic dendritic cell proliferation stimulated with LPS and ami-CD40 mAb, while it did not inhibit purified T cell activation, including CD 154 expression and IL-2 production. These results suggest that APC is dominant target cell population.