Phospholipase A2 activation by interleukin 1: Release and metabolism of arachidonic acid by IL 1-stimulated rabbit chondrocytes

Treatment of rabbit chondrocytes with natural or recombinant human IL 1 results in a dramatic dose-dependent increase in intracellular phospholipase A₂ (PLA₂) activity and subsequent secretion of this enzyme into the intracellular millieu. PLA₂ activity is detectable as early as 1 hr after IL 1 stimulation and is maximal by 24 hr. In the present study, we have characterized more fully the relationship between PLA₂ activation and arachidonate metabolism in these cells. IL 1 treatment of chondrocytes which had been prelabeled with ¹⁴C] arachidonic acid resulted in an enhanced release of free arachidonic acid identified by thin-layer chromatography. Moreover, the arachidonic acid liberated was subsequently metabolized exclusively to PGE₂; no significant increases in the production of 6-keto PGF₁, LTB₄, LTC₄, 12-HETE or 15-HETE were observed following IL 1 stimulation.