Inorganic Arsenic Activates Reduced NADPH Oxidase in Human Primary Macrophages through a Rho Kinase/p38 Kinase Pathway

摘要: Inorganic arsenic is an immunotoxic environmental contaminant to which millions of humans are chronically exposed. We recently demonstrated that human primary macrophages constituted a critical target for trioxide (As(2)O(3)), inorganic trivalent form. To specify the effects on macrophage phenotype, we investigated in present study whether As(2)O(3) could regulate activity NADPH oxidase, major superoxide-generating enzymatic system phagocytes. Our results show superoxide levels were significantly increased time-dependent manner blood monocyte-derived treated with 1 muM 72 h. Concomitantly, induced phosphorylation and membrane translocation oxidase subunit p47(phox) it also Rac1 p67(phox). Apocynin, selective inhibitor oxidases, prevented both production. activation was preceded by p38-kinase As(2)O(3)-treated macrophages. The SB-203580 subsequent Pretreatment Rho-kinase Y-27632 found mimic inhibitory prevent As(2)O(3)-induced p38 kinase. Treatment resulted secretion proinflammatory chemokine CCL18 fully inhibited apocynin SB-203580. Taken together, our demonstrate marked macrophages, likely through stimulation Rho-kinase/p38-kinase pathway, may contribute some deleterious phenotype.