Inhibition of interferon production by retinoic acid (vitamin A acid).

The production of interferon was employed to study the site and mechanism of action of retinoic acid (vitamin A). The data is consistent with a site of action of retinoic acid at the gene level, since it appears that interferon production is suppressed at the transcriptional step by a retinoic acid-induced protein. Evidence for this is as follows: (a) The effect of retinoic acid is probably on an early cellular function associated with interferon production rather than an effect on the inducer (virus or poly I:poly c). (b) The suppression of interferon production by retinoic acid is blocked by cycloheximide indicating a newly synthesized protein (repressor) mediates the suppression. (c) When allowances are made for the time required for the synthesis of the retinoic acid-induced protein, the time course of retinoic acid suppression of interferon production is superimposable on the time course of actinomycin D suppression since the slopes are very similar. These data provide the first evidence for transcriptional control of a specific protein (interferon) by retinoic acid. Additionally, they support the existence of transcriptional control of interferon production after inducer addition.