Effect of atrial natriuretic peptide on reactive oxygen species induced by hydrogen peroxide in THP-1 monocytes: Role in cell growth, migration and cytokine release

Atrial natriuretic peptide (ANP), a cardiovascular hormone, elicits different biological actions in theimmune system. The aim of the present study was to investigate in THP-1 monocytes the ANP effect on hydrogen peroxide (H2O2-induced Reactive Oxygen Species (ROS), cell proliferation and migration. A significant increase of H2O2-dependent ROS production was induced by physiological concentration of ANP (10−10 M). The ANP action was partially affected by cell pretreatment with PD98059, an inhibitor of mitogen activated-protein kinases (MAPK) as well as by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K) and totally suppressed by diphenylene iodonium (DPI), an inhibitor of the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The hormone effect was mimicked by cANF and an ANP/NPR-C signaling pathway was studied using pertussis toxin (PTX). A significant increase of H2O2-induced cell migration was observed after ANP (10−10 M) treatment, conversely a decrease of THP-1 proliferation, due to cell death, was found. Both ANP actions were partially prevented by DPI. Moreover, H2O2-induced release of IL-9, TNF-alpha, MIP-1alpha and MIP-1beta was not counteracted by DPI, whereas no effectwas observed in any experimental condition for both IL-6 and IL-1beta. Our results support the view thatANP can play a key role during the inflammatory process.