Regulation of LPS-mediated induction of C/EBP delta gene expression in livers of young and aged mice.

The C/EBP family of transcription factors plays a major role in the regulation of families of stress response genes, in particular, the acute phase response genes. We have examined expression of the C/EBP delta gene during the bacterial lipopolysaccharide mediated induction of the acute phase response in livers of young (4 months) and aged (24-28 months) male C57B1/6 mice by Northern, Western, and Southwestern analyses. C/EBP delta mRNA is present at a low constitutive level, is induced by lipopolysaccharide, and reaches the same induced level in young and aged mice. Aged mice, however, show a higher constitutive, uninduced mRNA pool level and a delay in recovery to uninduced levels after lipopolysaccharide treatment. C/EBP delta mRNA is observable 30 min after lipopolysaccharide in total RNA, cytoplasmic and polysomal fractions. Specific full length 28-kDa nascent peptides are detectable in polysomes 90 min after lipopolysaccharide. mRNA and nascent peptides cosediment with large polysomes and C/EBP delta mRNA is shifted to larger polysomes in lipopolysaccharide treated aged mice, consistent with an increased rate of initiation. Specific DNA-binding activity of C/EBP delta protein in nuclear extracts was examined by electromobility shift and antibody supershift assay. The levels of C/EBP delta binding-activity, are consistent with the changes in mRNA levels in young lipopolysaccharide treated livers. These studies support our hypothesis that aged mice exhibit a state of chronic inflammation or stress in the absence of a stressor.