IL-32? inhibits monocytic differentiation of leukemia cells by attenuating expression of transcription factor PU.1.

ABSTRACT: PU.1 is a key transcription factor regulating the myeloid differentiation. PU.1-induced monocytic differentiation into macrophage is also important for blood cancer development. Therefore, we chose THP-1 monocytic leukemia cells to investigate the function of a recently discovered IL-32?. Genetic analyses identified differences in the sequences of IL-32? and IL-32?. Using previously established cell lines that stably express IL-32? and IL-32? and cell lines transiently expressing IL-32?, we observed that expression of IL-32? inhibited phorbol 12-myristate 13-acetate (PMA)-induced monocytic differentiation in both THP-1 and HL-60 cells. IL-32? also suppressed expression of the macrophage cell surface markers, CD11b, CD18, and CD36. Interestingly, expression of IL-32? or IL-32? had no effect on the expression levels of cell cycle related factors. As a result, we concluded that these isoforms did not contribute to PMA-induced cell cycle arrest. IL-32? was found to modulate expression of PU.1, a transcription factor necessary for myeloid lineage commitment. Transient expression of PU.1 in THP-1/IL-32? cells rescued the observed differentiation defect. Additionally, transient expression of both CCAAT-enhancer-binding protein ? (C/EBP?) and PU.1 in THP-1/IL-32? cells exhibited synergistic effects in rescuing the differentiation defect. These observations indicate that intracellular IL-32? inhibits the differentiation of monocytes into macrophages by attenuating PU.1 expression.

SUBMITTER: Kim MS 

PROVIDER: S-EPMC4414198 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature