TRANSCRIPTION AND TRANSLATION ARE REQUIRED FOR FIBRINOGEN MESSENGER-RNA DEGRADATION IN HEPATOCYTES

Fibrinogen synthesis increases significantly during the early stages of an inflammatory reaction. In this study, we analysed quantitatively the fate of each fibrinogen transcript in primary rat hepatocytes during and following stimulation with interleukin-6 (IL-6). Northern blot hybridization analysis demonstrated a coordinated increase in the levels of fibrinogen mRNAs within 30 min following addition of IL-6. The half-life for each fibrinogen mRNA species was determined to be 8 h, and the decline in the level of all three fibrinogen transcripts occurred in a tightly coordinated fashion. When inhibitors of transcription (actinomycin-D) or translation (cycloheximide) were added following a maximal induction of fibrinogen mRNA expression by IL-6, the decay of mRNA was significantly diminished. Furthermore, the addition of cycloheximide (CHX) to hepatocytes increased fibrinogen mRNA levels, but only if the cells had been stimulated with IL-6. These data suggest that lability of the fibrinogen mRNAs may be due, in part, to the presence of a specific short-lived protein(s) that enhances their degradation. Constant exposure to IL-6 was required for the continual increase in expression of the fibrinogen mRNAs. Taken together, these results provide evidence that the turnover of fibrinogen mRNAs is stringently coordinated, and involves specific regulatory molecules yet to be characterized.