Synergistic Induction of Cyclooxygenase-2/Inducible Nitric Oxide Synthase Gene by Bacterial Lipopolysaccharide in Combinationwith Silica Parti-cles in RAW 264.7 Macrophages

Abstract

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are useful tool for the identification of inflammatory potentials of materials for medical device more specifically than present in vivo assays. The aim of the present study was to investigate the effects of silica particles on the expression of COX-2/iNOS mRNA gene in cultured murine macrophage cells. Silica particles significantly induced COX-2 and iNOS mRNA expression in RAW 264.7 macrophages in a dose-dependent manner. Additionally, in this study we demonstrated synergistic induction of the COX-2/iNOS mRNA expression by the combination of the lipopolysaccharide (LPS) with silica particles in RAW 264.7 cells. When the silica particles were added together with a minute amount of LPS, the levels of the COX-2 and iNOS mRNA expressions were increased several-fold greater than the addition of any inducer alone. This demonstrates that a concentration of LPS, such as would be found associated with a bacterial infection at the site of implanted biomaterials, induces a significant production of inflammatory mediators by macrophages.