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 will known that arachidonic acid, as a substrate of prostaglandi n G/H synthase (PGHS), is converted into prostaglandins of the two-ser ies. In this work, we attempted to determine whether arachidonic acid and prostaglandin E(2) might regulate the expression of PGHS and the p ancreatic-type phospholipase A(2)(PLA(2)I), which may be involved in t ile liberation of arachidonic acid from membrane phospholipids. For th is purpose, we used the uterine stromal cell line U-m, which produces prostaglandin E(2) and expresses both the constitutive and inducible P GHS enzymes (PGHS(1) and PGHS(2)) and PLA(2)I. The results show that P GHS(1), which is expressed at a high level in U-m cells, was not modif ied by arachidonic acid. The expression of PGHS(2) and PLA(2)I was up- regulated by increasing arachidonate concentrations (1-10 mu M). The m aximal 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 t o the control level. To discriminate between the effect of arachidonic acid and that of prostaglandins, which are highly increased in the pr esence of exogenous arachidonic acid, we treated the cells with two in hibitors of PGHS activity, aspirin and meclofenamic acid. Both inhibit ors failed to suppress the arachidonate-induced increase of PLA(2)I an d PGHS(2) expression and even enhanced it tither in the presence or ab sence 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 mu M . We conclude that arachidonic acid up-regulates the expression of PLA (2)I and PGHS(2) in the uterine stromal cells, independently of prosta noids, and that prostaglandin E(2) is capable of down-regulating enzym e expression.