Activin A and retinoic acid synergize in cyclooxygenase-1 and thromboxane synthase induction during differentiation of J774.1 macrophages.

ABSTRACT

The murine macrophage cell line J774.1 was used to study the development of prostanoid biosynthesis under the influence of activin A and retinoic acid. Treatment of cells with 3 nM activin A for 48 h increased the biosynthesis of the prostaglandins E2, D2, F2 alpha and thromboxane A2 more than fourfold due to an induction of cyclooxygenase-1 while cyclooxygenase-2 was unaffected. Transforming growth factor-beta acted in a similar way. Retinoic acid, when present alone, was without effect on the total cyclooxygenase products and only slightly changed the pattern of prostanoids. However, when coincubated with activin A, retinoic acid specifically induced the synthesis of thromboxane-A-synthase-specific mRNA and induced an increase in enzyme activity with a synergistic effect on cyclooxygenase-1 protein and mRNA. JunB, but not c-jun, mRNA expression was found under these conditions in addition to a transient c-fos mRNA increase. The combination of activin A and retinoid acid may be regarded as a differentiation model to study the development of cell-specific prostanoid patterns in macrophages and possibly other differentiating cells.