C-REACTIVE PROTEIN AND SERUM AMYLOID A MESSENGER-RNA STABILITY FOLLOWING INDUCTION BY CYTOKINES

We determined the effects of cytokine withdrawal on C-reactive protein (CRP) and serum amyloid A (SAA) mRNA abundance in Hep3B cells followi ng 24 h of preinduction with interleukin 6 plus interleukin 1 beta. Af ter cytokine withdrawal, CRP transcription rate rapidly fell to undete ctable levels and mRNA levels fell with a half-disappearance time of a bout 2.5 h, In view of the relatively small amount of CRP transcriptio n occurring at this time, it is likely that this value closely reflect s the actual half-life of CRP mRNA, In contrast, substantial SAA trans cription continued for at least 8 h, while SAA mRNA fell with a half-d isappearance time of about 8.5 h, It is not possible, under these cond itions, to determine SAA mRNA half-life, but it clearly was no greater than 8.5 h, Both Actinomycin D (ActD) and cycloheximide enhanced the stability of SAA mRNA, strongly suggesting that SAA mRNA degradation r equires synthesis of a short-lived protein, CRP mRNA stability was als o enhanced by ActD, but cycloheximide did not have a protracted stabil izing effect, suggesting complex regulatory processes. These studies p rovide insight into the stability of CRP and SAA mRNA following induct ion with [IL-6 + IL-1 beta] and into the mechanisms regulating their d egradation. (C) 1996 Academic Press Limited