Arachidonic Acid Up‐Regulates and Prostaglandin E 2 Down‐Regulates the Expression of Pancreatic‐Type Phospholipase A 2 and Prostaglandin‐Endoperoxide Synthase 2 in Uterine Stromal Cells

It is well known that arachidonic acid, as a substrate of prostaglandin G/H synthase (PGHS), is converted into prostaglandins of the two‐series. In this work, we attempted to determine whether arachidonic acid and prostaglandin E 2 might regulate the expression of PGHS and the pancreatic‐type phospholipase A 2 (PLA 2 I), which may be involved in the liberation of arachidonic acid from membrane phospholipids. For this purpose, we used the uterine stromal cell line U 111 which produces prostaglandin E 2 and expresses both the constitutive and inducible PGHS enzymes (PGHS 1 and PGHS 2 ) and PLA 2 I. The results show that PGHS 1 which is expressed at a high level in U 111 cells, was not modified by arachidonic acid. The expression of PGHS 2 and PLA 2 I was up‐regulated by increasing arachidonate concentrations (10–10 μM). The maximal response was obtained at 24 h, reaching a 2.3‐fold and 2.6‐fold increase for PGHS 2 and PLA 2 I expression, respectively, compared to the control level. To discriminate between the effect of arachidonic acid and that of prostaglandins, which are highly increased in the presence of exogenous arachidonic acid, we treated the cells with two inhibitors of PGHS activity, aspirin and meclofenamic acid. Both inhibitors failed to suppress the arachidonate‐induced increase of PLA 2 I and PGHS 2 expression and even enhanced it either in the presence or absence of arachidonic acid. In contrast, the addition of prostaglandin E 2 to the culture medium decreased the expression of both enzymes in a dose‐dependent manner, the maximal response being reached at 1 μM. We conclude that arachidonic acid up‐regulates the expression of PLA 2 I and PGHS 2 in the uterine stromal cells, independently of prostanoids, and that prostaglandin E 2 is capable of down‐regulating enzyme expression.