Activation of the arachidonic acid cascade by interleukin-1 in human chondrocytes

The arachidonic acid cascade in interleukin-1-stimulated chondrocytes was investigated by studying the activation of phospholipase A₂ and the regulation of cyclooxygenase. IL1 stimulated the [³H]-arachidonic acid release and analyses of the [³H]-arachidonic acid-derived metabolites stressed that most of the released radioactivity after IL1 activation was associated with prostaglandin E₂. Human IL1-stimulated chondrocytes also synthesized prostaglandin F(2α) and 6-keto-prostaglandin F(1α). Using transcription and translation inhibitors it was shown that protein synthesis was required for PG synthesis. Aspirin, a specific inhibitor of cyclooxygenase, was also used and confirmed that the production of PG induced by IL1 is imputable to a de novo synthesis of cyclooxygenase. In human chondrocytes, cyclooxygenase is thus a key enzyme in the AA cascade in addition of PLA₂.