Activated macrophages contribute to chronic inflammation by the secretion of cytokines and proteinases. Tumor necrosis factor α (TNFα) is particularly important in this process because of its ability to regulate other inflammatory mediators in an autocrine and paracrine fashion. The mechanism(s) responsible for the cell type-specific regulation of TNFα is not known. We present data to show that the expression of TNFα is regulated by the transcription factor C/EBPβ (NF-IL6). C/EBPβ activated the TNFα gene promoter in cotransfection assays and bound to it at a site which failed to bind the closely related protein C/EBPα. Finally, a dominant-negative version of C/EBPβ blocked TNFα promoter activation in myeloid cells. Our results implicate C/EBPβ as an important regulator of TNFα by myelomonocytic cells.
- transcription factor
ASJC Scopus subject areas