Identification of novel pharmacological activities of an antifungal agent, nystatin, to promote dendritic cell maturation.

As an unbiased functional screen to identify agents activating dendritic cells (DCs), we recently developed a DC-based biosensor system, in which a stable murine DC line XS106 was engineered to express the yellow fluorescent protein (YFP) gene under the control of the IL-1beta promoter. Here we report that nystatin (NYT), an antifungal drug of the family of polyene macrolide antibiotics, elevated YFP expression by the resulting XS106-pIL1-YFP DC biosensor clone in a dose-dependent fashion. With respect to the underlying mechanisms, NYT activated the NFkappaB p65 and c-Rel subunits in the parental XS106 DC line. Moreover, NYT dose-dependently increased the surface expression of major histocompatibility complex (MHC) class II (MHC II), CD40, CD54, CD80, and CD86 by murine bone marrow-derived DCs and triggered their robust production of IL-1beta, IL-6, IL-12, tumor necrosis factor alpha, and macrophage inflammatory protein-1alpha. Our results document previously unrecognized pharmacological activities of the most commonly used antifungal drug to promote DC maturation.