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 re gulation of families of stress response genes, in particular, the acut e phase response genes. We have examined expression of the C/EBP delta gene during the bacterial lipopolysaccharide mediated induction of th e acute phase response in livers of young (4 months) and aged (24-28 m onths) male C57B1/6 mice by Northern, Western, and Southwestern analys es. C/EBP delta mRNA is present at a low constitutive level, is induce d by lipopolysaccharide, and reaches the same induced level in young a nd aged mice. Aged mice, however, show a higher constitutive, uninduce d mRNA pool level and a delay in recovery to uninduced levels after li popolysaccharide treatment. C/EBP delta mRNA is observable 30 min afte r lipopolysaccharide in total RNA, cytoplasmic and polysomal fractions . Specific full length 28-kDa nascent peptides are detectable in polys omes 90 min after lipopolysaccharide. mRNA and nascent peptides cosedi ment with large polysomes and C/EBP delta mRNA is shifted to larger po lysomes in lipopolysaccharide treated aged mice, consistent with an in creased rate of initiation. Specific DNA-binding activity of C/EBP del ta protein in nuclear extracts was examined by electromobility shift a nd antibody supershift assay. The levels of C/EBP delta binding-activi ty, are consistent with the changes in mRNA levels in young lipopolysa ccharide treated Livers. These studies support our hypothesis that age d mice exhibit a state of chronic inflammation or stress in the absenc e of a stressor. (C) 1998 Elsevier Science B.V. All rights reserved.