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Updated: Aug 11, 2026

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages
Published on: November 3, 2014
Cytokines induce an L-arginine-dependent effector system in nonmacrophage cells
I J Amber1, J B Hibbs, R R Taintor
1VA Medical Center, Salt Lake City, UT 84148.
Abstract:
Treatment of EMT-6 mammary adenocarcinoma cells with gamma interferon (rMuIFN gamma) plus tumor necrosis factor (rMuTNF alpha) and/or interleukin-1 (rHuIL-1 alpha) 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 rMuIFN gamma. 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.
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