THE SPONTANEOUS EXPRESSION OF INTERLEUKIN-1-BETA AND INTERLEUKIN-6 ISASSOCIATED WITH SPONTANEOUS EXPRESSION OF AP-1 AND NF-KAPPA-B TRANSCRIPTION FACTOR IN ACUTE MYELOBLASTIC-LEUKEMIA CELLS

The nature of the spontaneous expression of cytokines that is observed in blasts of some AML patients is unclear. We studied whether or not the spontaneous expression of IL-1 beta and IL-6 is due to an increase d transcription rate of the cytokine gene and associated with a sponta neous expression of two transcription factors that play an important r ole in IL-1 beta and IL-6 gene transcription, namely activator protein -1 (AP-1) and nuclear factor-kappa B (NF-KB). In eight of the 19 AML p atients a spontaneous expression of IL-1 beta mRNA was observed, where as IL-6 mRNA was expressed in seven of the cases. Expression of IL-6 m RNA correlated nicely with the secretion of IL-6 protein. Nuclear run- on experiments showed that spontaneous expression of IL-1 beta and IL- 6 was at least partly due to an increased transcription rate of the re spective genes compared to the results from healthy unstimulated monoc ytes. Electrophoretic mobility shift assays demonstrated that especial ly spontaneous expression of NF-KB is associated with spontaneous cyto kine expression. However, the spontaneous expression of transcription factors is not due to the endogenous secretion of IL-1 since the addit ion of anti-IL-1 monoclonal antibody did not affect the expression of NF-KB. Finally, supershift experiments were performed that demonstrate d that the NF-KB consists of the p50 and the p65 subunits. In summary, these results demonstrate that the spontaneous expression of cytokine s is frequently associated with an increased transcription rate and a spontaneous expression of transcription factors.