Retinoic acid-induced expression of tissue transglutaminase in mouse peritoneal macrophages

The culture of peritoneal macrophages in serum-containing media induces a dramatic increase in the expression of the enzyme tissue transglutaminase. The transglutaminase-inducing activity of serum is abolished by extraction of lipids and fully restored by readdition of physiological concentrations (1-100 nM) of trans-retinoic acid. Induction of the enzyme is detectable within a 90-min exposure of macrophages to retinoic acid and is completely blocked by actinomycin D, suggesting that the retinoid rapidly increases the rate of transglutaminase gene expression. Delipidized serum is required to elicit the transglutaminase-inducing activity of retinoic acid and this effect is decreased if the serum is depleted of the serum retinol-binding protein. Our studies suggest that retinoic acid and serum retinol-binding protein can directly regulate macrophage gene expression and specifically induce the synthesis of tissue transglutaminase.