B-cell activating factor (BAFF) is a potent cell-survival factor, expressed in many hematopoietic cells, for B-cell maturation and activation. It is involved in pathogenesis of autoimmune disorders and B-cell malignancies. Although BAFF is produced by interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in monocytes, the mechanisms of the modulation of BAFF production and expression under normal and pathologic conditions have not been completely elucidated. In this study, we examined the effects of several inflammatory cytokines on BAFF expression in cultured human promyelocytic leukemia (HL-60) cells both at the transcriptional and posttranscriptional level. Incubation of the cells with IL-10 and IFN-gamma elevated the expression of membrane-bound and soluble forms of BAFF. A similar increase in BAFF-specific mRNA was noted in cultured cells. Unexpectedly, interleukin-4 (IL-4) treatment hardly affected BAFF expression at the mRNA and protein levels. Transcriptional regulation was examined in cultures transfected with a human BAFF promoter/reporter gene (chloramphenicol acetyltransferase) construct. IL-10 and IFN-gamma elicited marked enhancement of the human BAFF promoter activity. Collectively, these results demonstrated that IL-10 and IFN-gamma both regulate BAFF expression and synthesis in human promyelocytic leukemia cell cultures, and the activation occurs at the transcriptional level.