Modulation of transforming growth factor beta-1 gene expression by interleukin-12

The interaction of cytokines and their net balance with regard to macrophag e activation (or deactivation) and immune stimulation (or suppression), ult imately determines the success of host-immune response at sites of active i nfection. A regulatory role for interleukin (IL)-12 in production of transf orming growth factor (TGF)-beta 1 has been suggested, however, remains cont roversial. In this study, we analyzed the effect of IL-12 on TGF-beta 1 exp ression in the human lines, K562 and A549, and in primary human monocytes a nd macrophages. We found that IL-12 down-regulates TGF-beta 1 mRNA expressi on in K562, monocytes and bone marrow cells, and to a lesser extent in the A549 cells. Using constructs containing different regions of the first prom oter of the TGF-beta 1 gene and a reporter gene, we also demonstrate that t his effect is mediated through the TGF-beta 1 gene promoter in the K562 and monocytic cell types. In conclusion, the critical role of IL-12 in the ear ly activation of the immune response to pathogens may include down-modulati on of TGF-beta 1 gene activity.