Synergistic Effect of Interleukin-1β and Tumor Necrosis Factor α on PGE2Production by Articular Chondrocytes Does Not Involve PLA2Stimulation

Abstract

This study investigates the ways in which two proinflammatory cytokines, tumor necrosis factor α (TNF) and interleukin-1β (IL1), cause increased production of prostaglandin E2(PGE2) in rabbit articular chondrocytes (RAC). Rabbit articular chondrocytes in primary culture were incubated with IL1, TNF, or both. Arachidonic acid (AA) release, PGE2production, and the activities of cytosolic phospholipase A2(cPLA2), secreted phospholipase A2(sPLA2), and cyclooxygenase (COX) were measured. The mRNA levels of cPLA2, sPLA2, and COX-2 were also measured by Northern blotting, using specific complementary DNA probes. Incubation of IL1-stimulated RAC with TNF further increased PGE2production. This synergy did not involve PLA2stimulation, as there were no increases in AA release, cPLA2and sPLA2activities, or mRNA. In contrast, TNF increased the effect of IL1 on COX-2 activity and mRNA level. These results show that TNF and IL1 act in synergy in PGE2production in articular chondrocytes. As sPLA2and cPLA2do not seem to be involved, COX-2 appears to be the best target for a specific anti-inflammatory strategy against cartilage degradation.