C EBP-BETA IS REQUIRED FOR THE LATE PHASES OF ACUTE-PHASE GENES INDUCTION IN THE LIVER AND FOR TUMOR-NECROSIS-FACTOR-ALPHA, BUT NOT INTERLEUKIN-6, REGULATION/

C/EBP beta is a leucine-zipper transcription factor believed to play a n important role in the control of liver functions, and in particular in the transcriptional regulation of acute phase genes in response to several inflammatory stimuli and to recombinant cytokines. Moreover, t his factor has been proposed as an important activator of several cyto kine genes. We recently described the generation of mice in which the C/EBP beta gene has been inactivated by gene targeting, showing that t hey are viable, but present specific defects in the myeloid and lympho id compartments. Here we demonstrate that C/EBP beta does indeed play a role in the transcriptional induction of some, but not all, liver ac ute phase genes. Activation is in particular defective in C/EBP beta-d eficient mice in the later phases of induction, suggesting that the ea rly phases may be triggered by factors other than C/EBPs. Moreover, IL -6 activation is normal and TWF alpha activation is defective in the m utant mice, indicating a differential role of C/EBP beta in the contro l of these two cytokines' production.