SHORT COMMUNICATION: Cytokines Induce an L-Arginine-Dependent Effector System in Nonmacrophage Cells

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Abstract
Treatment of EMT-6 mammary adenocarcinoma cells with gamma interferon (rMuIFNγ) plus tumor necrosis factor (rMuTNFα) and/or interleukin-1 (rHuIL-1α) causes release of iron-55 label, inhibition of DNA replication, and inhibition of aconitase activity. In addition, the same combinations of cytokines induce EMT-6 cells to synthesize L-citrulline, nitrite, and nitrate directly from L-arginine. Lipopolysaccharide (LPS) can act as a cofactor in the induction of these metabolic effects when added to EMT-6 cells in the presence of rMuIFNγ. The results show that increased levels of cytokines in the microenvironment can induce a novel effector pathway in somatic cells not specialized for host defense, resulting in specific metabolic effects as well as the inhibition of cellular proliferation.