Effect of interleukin 1, lipopolysaccharide and phorbol esters on phospholipase D activity in chondrocytes

Phorbol 12-myristate 13-acetate (PMA), interleukin-1 (IL-1) and lipopolysaccharide (LPS) induce similar responses in a variety of cell types, including chondrocytes. These responses include the release of arachidonic acid (AA) and the production of prostaglandin E2 (PGE2). Although PMA is known to stimulate phospholipase D (PLD) activity in most cells, it is not known whether LPS and IL-1 also stimulate PLD activity, or whether PLD activity contributes to AA liberation and PGE2 production in chondrocytes. In the present study we compared the effect of IL-1, LPS and protein kinase C (PKC) activators (PMA), mezerein, phorbol dibutyrate on PGE2 synthesis and PLD activity in articular chondrocytes. Although IL-1, LPS and PKC activators stimulate PGE2 synthesis, only the PKC activators stimulated PLD activity. The PKC inhibitor, staurosporine, as well as PKC downregulation, were both found to inhibit PMA-induced PLD activity without inhibiting other PMA-induced effects in chondrocytes. Our data suggest that although chondrocytes contain a PKC-regulated PLD activity, this is not a possible mechanism by which IL-1 or LPS stimulate early events in these cells.