Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cell
The main activity of mycophenolic acid (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.
Dorota Iwaszkiewicz-Grześ, Grzegorz Cholewiński, Agata Kot-Wasik, Potr Trzonkowski, Krystyna Dzierzbicka. (2017). Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cell. International Immunopharmacology, 44, 137-142. https://doi.org/10.1016/j.intimp.2017.01.011
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