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Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation


ASPIRIN prevents prostaglandin (PG) generation by directly inhibiting the cyclo-oxygenase enzyme responsible for PG biosynthesis1–3. In addition, there is now conclusive evidence that anti-inflammatory steroids can also prevent PG generation4–13. Unlike the aspirin-like drugs, steroids have no anti-cyclo-oxygenase activity but exert their action by preventing the release from phospholipids of the fatty acid substrates required for PG biosynthesis4–9,12,13. We have shown that stimulation of thromboxane A2 (TXA2) release by agents such as histamine, 5-hydroxytryptamine and rabbit aorta contracting substance-releasing factor (RCS–RF) (but not arachidonic acid) is inhibited by anti-inflammatory steroids, and that their potency in this action closely parallels their anti-inflammatory activity12,13. Furthermore, their mechanism of action involves the inhibition of phospholipase A2 activity, and thus of arachidonate release within the lung12,13. In several other tissues, the mechanism of steroid hormone action depends on the combination of thesteroid with a cytosolic receptor protein, the translocation of this drug–receptor complex to the nucleus and the initiation of protein biosynthesis14–16. We now show that similar events occur in the guinea pig perfused lung before inhibition by steroids of phospholipase A2 activity (and thus TXA2 generation). We have discovered a steroid-induced factor which mimics the anti-phospholipase effects of these anti-inflammatory agents.

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FLOWER, R., BLACKWELL, G. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature 278, 456–459 (1979).

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