Copper oxide nanoparticles recruit macrophages and modulate nitric oxide, proinflammatory cytokines and PGE(2) production through arginase activation

Abstract

Aim: In the present study, we examine the effects of copper oxide nanoparticles (CuNP) on macrophage immune response and the signaling pathways involved. Materials & Methods: 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. Results: 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 TNF alpha and MIP-1 beta production. In addition, CuNP induced the expression of COX-2 and the production of PGE(2) through arginase activation. Conclusion: Our results demonstrate that CuNP activate arginase and suppress macrophage innate immune response.