REGULATION OF THE TRANSCRIPTION FACTOR C EBP-ALPHA FOLLOWING PERITONEAL SEPSIS/

The transcription factors C/EBP alpha and C/EBP beta belong to the leu cine-zipper C/EBP (CCAAT/enhancer binding protein) family of DNA-bindi ng proteins. C/EBP alpha and C/EBP beta are expressed in the liver and are implicated in the control of transcriptional events following sep sis. It is hypothesized that inhibition of C/EBP alpha gene expression following sepsis may lead to some of the phenotypic features we recog nize as sepsis syndrome such as decreased visceral protein (albumin) s ynthesis. In this study we demonstrate that C/EBP alpha mRNA accumulat ion is transiently inhibited 12 hr following peritoneal insult, consis tent with previous data, However, we demonstrate that (1) there is inc reased binding of hepatic nuclear protein to the C/ EBP alpha DNA resp onse element 48 hr following insult, (2) a marked increase in C/EBP al pha protein is observed 48 hr following CLP insult compared with no in crease in hepatic C/EBP alpha protein at 12 hr postinsult, (3) the inc rease in hepatic C/EBP alpha protein at 48 hr following cecal ligation and puncture is not associated with an increase in C/EBP alpha: mRNA accumulation, (4) the increase in hepatic C/EBP alpha protein is assoc iated with an increase in C/EBP beta protein, and (5) hepatic albumin mRNA accumulation is decreased at 12 and 48 hr following insult and do es not correlate with the C/EBP alpha protein synthesis. We conclude t hat the possible role of the transcription factor C/EBP alpha with res pect to decreased albumin gene expression following sepsis must be ree valuated. (C) 1995 Academic Press, Inc.