title: Amphotericin B activation of human genes encoding for cytokines.
abstract: Amphotericin B has been shown to cause release of cytokines, including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), from monocytes and macrophages. Human and murine monocytic cell lines were used to evaluate the effects of amphotericin B on the transcription of IL-1alpha, IL-1beta, and TNF-alpha and the transcription and production of soluble IL-1 receptor antagonist (sIL-1Ra). The effects of inhibitors of transcription and translation on amphotericin B-induced IL-1beta expression in a human monocytic cell line were also evaluated. Amphotericin B markedly increased IL-1beta and TNF-alpha mRNA levels, with peak levels occurring by 4 h. Amphotericin B induced production of sIL-1Ra in a dose-dependent fashion and induced sIL-1Ra mRNA, with peak levels at 24 h. Cycloheximide and actinomycin D resulted in a dose-dependent decrease in amphotericin B-induced IL-1beta expression at 2 h. Thus, amphotericin B induces gene expression for IL-1beta, TNF-alpha, and IL-1Ra in human and murine monocytic cells.
authors.affiliation: Department of Clinical Pharmacy Practice, University of Mississippi Medical Center, Jackson, Mississippi, 39216-4505, USA. drogers@medicine.umsmed.edu
authors.forename: P D
authors.initials: PD
authors.lastname: Rogers
authors.forename: J K
authors.initials: JK
authors.lastname: Jenkins
authors.forename: S W
authors.initials: SW
authors.lastname: Chapman
authors.forename: K
authors.initials: K
authors.lastname: Ndebele
authors.forename: B A
authors.initials: BA
authors.lastname: Chapman
authors.forename: J D
authors.initials: JD
authors.lastname: Cleary
mesh_terms: D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide