Copper oxide nanoparticles recruit macrophages and modulate nitric oxide, proinflammatory cytokines and PGE2 production through arginase activation

In the present study, we examine the effects of copper oxide nanoparticles (CuNP) on macrophage immune response and the signaling pathways involved. A peritonitis model was used to determine in vivo immune cells recruitment, while primary macrophages were used as an in vitro model for the cellular and molecular analysis. In vivo, CuNP induce significant macrophages recruitment to the site of injection. In vitro, in LPS-stimulated primary macrophages, the co-treatment with CuNP inhibited the production of NO in a dose-dependent manner. The mechanism underlying NO and proinflammatory cytokines inhibition was associated with an increased arginase activity. Macrophage stimulation with CuNP did not provoke any cytokine secretion; however, arginase inhibition promoted TNFα and MIP-1β production. In addition, CuNP induced the expression of COX-2 and the production of PGE2 through arginase activation. Our results demonstrate that CuNP activate arginase and suppress macrophage innate immune response.