Role of IL-1 beta and corticosteroids in the regulation of the C/EBP-alpha, beta and delta genes in vivo.

We have examined the regulatory effects of interleukin 1 beta (IL-1 beta) on the activation of three different isoforms of the C/EBP family of transcription factors (alpha, beta and delta), in hepatocytes of normal and adrenalectomized (ADX) rats. C/EBP-beta and delta mRNA levels were enhanced by IL-1 beta, whereas that of C/EBP-alpha was not affected by treatment with this interleukin in both normal and adrenalectomized rats. The magnitude of the induction was strikingly higher for C/EBP delta in adrenalectomized animals, indicating a suppressive effect of corticosteroids in the IL-1 beta regulatory pathway. The pattern of C/EBP protein synthesis did not always reflect the mRNA findings. For C/EBP-alpha the protein synthesis was higher than expected in IL-1 beta treated ADX animals compared to normal rats. The pattern of C/EBP synthesis was the one that better reflected the pattern of the mRNA transcription. Differently, the induction of C/EBP-delta was not as pronounced as that of the corresponding mRNA in IL-1 beta treated ADX rats. Hormonal modulation of C/EBP transcription factors was studied in parallel with the hormonal induction of the Alpha-1-Acid Glycoprotein (AGP) gene, which is known to be highly induced in rat liver during the acute phase response. This short report also indicates an important role of corticosteroids in the regulation of transcription factors involved in IL-1 beta signalling during the acute phase response.