Prostaglandin production by human trabecular cells: in vitro inhibition by dexamethasone.
In addition to the well-known ability of prostaglandins (PGs) to raise intraocular pressure (IOP), it recently has been reported that moderate and low doses of PGE2 and PGF2 alpha significantly reduce IOP in a variety of experimental animals. These studies suggested to us that PGs might serve as endogenous regulators of outflow facility in the meshwork if these autacoids were produced and secreted by human trabecular cells. To examine this possibility, media from well-defined trabecular cell material were assayed using specific radioimmunoassays. Morphologically differentiated human trabecular cells produced high levels of PGE2, and somewhat lower levels of PGF2 alpha and 6KF1 alpha in the presence and absence of serum. In a typical experiment, the following PG levels were detected in the cell culture media after 24 hours: PGE2; 225; PGF2 alpha, 33.5; 6KF1 alpha, 12.7 ng/ml with the presence of 10% fetal calf serum; and PGE2, 30.0; PGF2 alpha, 4.8; 6KF1 alpha, 3.6 ng/ml in serum-free media. Since glucocorticoids are known to inhibit PG pathways in other tissues, this effect was examined in the cultured trabecular cells. Moderate concentrations of dexamethasone (DEX) produced a marked inhibition in the levels of all three PGs. For PGE2 production, 10(-8) M DEX inhibited approximately 75%, and 10(-7) M DEX inhibited approximately 90%. More detailed dose-response studies revealed that the I50 for inhibition of PG production by dexamethasone was less than 10 nM, thus indicating that the steroid effect probably involved high affinity glucocorticoid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
D000527:Alprostadil / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007429:Intraocular Pressure; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011863:Radioimmunoassay; D014129:Trabecular Meshwork / Q000378:metabolism*
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; C022950:6-ketoprostaglandin E1; D003907:Dexamethasone; D015237:Dinoprost; D000527:Alprostadil; D015232:Dinoprostone; C100006:prostaglandin F1