Titanium-alloy particles induced cyclooxygenase-2 in human macrophage-like cells in vitro

Prostaglandin E2 (PGE2) has been reported to be an important mediator in aseptic loosening and/or periprosthetic osteolysis in total joint arthroplasties. Previous studies have reported that human macrophages stimulated with particles in vitro release PGE2. However, they have not shown the expression of cyclooxygenases (COX) which are rate-limiting enzymes of PGE2 synthesis. We hypothesized that PGE2 production by activated macrophages is dependent upon the induction of COX-2, not upon the constitutive isozyme, COX-1. When we evaluated the expression of COX-1 and COX-2 in titanium-alloy particle-stimulated human macrophages, the expression of COX-2 mRNA was up-regulated by the particles, on the other hand, the expression of COX-1 mRNA was not affected. In addition, NS-398, a COX-2 inhibitor drastically suppressed up-regulated PGE2 production by the particles. These results provide strong evidence that PGE2 production by particle-stimulated macrophages is dependent upon the induction of COX-2, not COX-1.