The transcription factor C/EBP beta is essential for inducible expression of the cox-2 gene in macrophages but not in fibroblasts

Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme for the inducible synt hesis of prostaglandins, and its up-regulated activity is thought to play a pathological role in diseases such as inflammatory bowel disease, rheumato id arthritis, and cancer. Regulation of COX-2 expression is complex and app ears to involve diversified mechanisms in different cell types and conditio ns. Here we make use of immortalized macrophages and fibroblasts that we ha ve generated from C/EBP beta -deficient mice to directly test and compare t he specific role played by this factor in inducible COX-2 expression in the se two cell types. We could demonstrate that COX-2 mRNA induction and promo ter activity were profoundly impaired in C/EBP beta (-/-) macrophages and c ould be rescued by expression of C/EBP beta. The obligatory role of C/EBP b eta in COX-2 expression appeared to be mediated exclusively by the C/EBP el ement located at positions -138/-130 of the murine cox-2 promoter; arid did not involve altered activity at the level of the other promoter elements d escribed previously (the -402/-392 NF-kappaB site, the -59/-48 CRE/E box el ement, and a potential second C/EBP site located at positions -93/-85). In contrast, COX-2 induction was completely normal in C/EBP beta -deficient fi broblasts, thus highlighting the diversity of cell-specific molecular mecha nisms in determining inducible COX-2 expression and prostaglandins producti on.