Induction by interleukin-1 (IL-1) of the mRNA of histidine decarboxylase, the histamine-forming enzyme, in the lung of mice in vivo and the effect of actinomycin D.

It is known that the activity of histidine decarboxylase (HDC), the histamine-forming enzyme, is induced in response to various stimuli. However, it has repeatedly been reported that actinomycin D (Act D), a typical inhibitor of RNA synthesis, is either ineffective, or actually potentiates induction of this enzyme. Thus, it has been suggested that the induction of HDC may not require the formation of mRNA, i.e. that pre-formed, long-lived mRNA molecules may be responsible for the induction. In the present study, we examined the effects of interleukin-1alpha (IL-1alpha) on the amount of HDC mRNA present during the induction of HDC activity. In mice injected with IL-1alpha, HDC mRNA increased in the lung, spleen and stomach, but was hardly detectable in these tissues in control (saline-injected) mice. In the lung, the time course of the rise and fall in HDC mRNA was shorter than that of the rise and fall in HDC activity. In the present study, actinomycin D (Act D) did not inhibit the increase in HDC mRNA induced by IL-1alpha; in fact, it potentiated the elevation of both HDC mRNA and HDC activity. These results suggest that IL-1alpha induces HDC activity or its enzyme protein through the formation of short-lived HDC mRNA molecules. This is the first demonstration that Act D can enhance an increase in HDC mRNA: this potentiating, rather than inhibiting, effect is discussed.