C EBP-BETA REGULATION OF THE TUMOR-NECROSIS-FACTOR-ALPHA GENE/

Activated macrophages contribute to chronic inflammation by the secret ion of cytokines and proteinases. Tumor necrosis factor alpha (TNF alp ha) is particularly important in this process because of its ability t o regulate other inflammatory mediators in an autocrine and paracrine fashion. The mechanism(s) responsible for the cell type-specific regul ation of TNF alpha is not known. We present data to show that the expr ession of TNF alpha is regulated by the transcription factor C/EBP bet a (NF-IL6). C/EBP beta activated the TNF alpha gene promoter in cotran sfection assays and bound to it at a site which failed to bind the clo sely related protein C/EBP alpha. Finally, a dominant-negative version of C/EBP beta blocked TNF alpha promoter activation in myeloid cells. Our results implicate C/EBP beta as an important regulator of TNF alp ha by myelomonocytic cells.