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.
Ogawa
Yasushi
Y
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Mizumoto
Norikatsu
N
Tanaka
Hiroaki
H
Matsushima
Hironori
H
Takashima
Akira
A
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D009761:Nystatin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
D000935:Antifungal Agents; D015703:Antigens, CD; D001426:Bacterial Proteins; D016207:Cytokines; D007375:Interleukin-1; D008164:Luminescent Proteins; D020569:Proto-Oncogene Proteins c-rel; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C054562:yellow fluorescent protein, Bacteria; D009761:Nystatin