تنظيم ترشح پروستاگلاندين E2 توسط مهارگران آنزيم هاي سيكلواكسيژناز (نوع I و )II و پروستاگلاندين دهيدروژناز در سلول هاي تروفوبلاست جفت انساني

Recent studies in amnion and chorion trophoblasts have shown that glucocorticoids (GC) increase and decrease expression and activity of PGHS and PGDH enzymes respectively. However, the effects of GC on the expression of these enzymes in placental cells (PC) is unknown. Human placenta were obtained from uncomplicated term pregnancies after elective cesarian section delivery. The dispresed cells were filtered and loaded on to a continous percoll gradient (5-70%) and after 72 hrs incubation of primary culture cell medium were washed and changed and then treated for 24 hrs in the presence or absence of arachidonic add (5µM), plus various combinations of meloxicam (MEL , 1µM), indomethacin (Ind , 1µM) dexamethasone (DEX , 1 µM) and sulphasalazine (SFZ , 11.LM). After incubation period cell mediums were collected for determination of PGE2 by radioirnmunoassay. One-way ANOVA test and studentʹs t-test were used to assess statistical differences and ststistical significances were set at P<0.05. Dexamethasone produced a significant , almost doubling of PGE2 output , but this was not altered further by Mel. In the presece of SFZ alone , there was a significant approximate doubling increase in the output of PGE2 (P<0.05) and this increase further in the presence of dexamethasone that increase was reduced by further addition of Mel (P<0.05) . Indomethacine treatment significantly reduced stimulation of PGE2 output seen in the presence of SFZ , or the further increase seen in cells treated with SFZ plus dexamethasone. We conclude that basal PGE2 output by term human PC likely depends on the activity of PGHS- 1 not PGHS-2 .The effects of SFZ show the importance of endogenous PGDH in regulating PGE2 output , and interactions with SFZ , DEX and MEL suggest that GC stimulated output of PGE2 by PC may be attributable to both up regulation of PGHS and decrease activity of PGDH.