Interleukin 1 and phorbol 12-myristate 13-acetate induce collagenase and PGE 2 production through a PKC-independent mechanism in chondrocytes

Abstract

In the present study we demonstrate that interleukin 1 (IL 1) and phorbol 12-myristate 13-acetate (PMA) stimulate collagenase production by bovine chondrocytes in monolayer culture. Since it has been well established that PMA stimulates protein kinase C (PKC), we examined whether IL 1 and PMA also stimulate PKC in chondrocytes. In agreement with other studies, PMA induced the translocation of PKC, reflecting PKC activation by PMA. In contrast, IL 1 did not induce the translocation of PKC. Both IL 1 and PMA stimulated the release of [ 14C]arachidonic acid from chondrocyte phospholipids, suggesting that both agents stimulate phospholipase A 2 (PLA 2). Concomitantly, IL 1 and PMA also induced a pronounced increase in the production of PGE 2. Pre-incubation of chondrocytes with staurosporine, a PKC inhibitor, did not affect the stimulation of collagenase production by IL 1 and only minimally that induced by PMA. Similarly, high concentrations of staurosporine did not inhibit prostaglandin E 2 (PGE 2) production induced by IL 1 or PMA. These data show that IL 1 and PMA stimulate the PLA 2 pathway and collagenase production, however, these processes can occur in the absence of PKC activation.