Cytokines induce an L-arginine-dependent effector system in nonmacrophage cells.
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.
Amber
I J
IJ
VA Medical Center, Salt Lake City, UT 84148.
Hibbs
J B
JB
Taintor
R R
RR
Vavrin
Z
Z
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001688:Biological Products / Q000494:pharmacology*; D002956:Citrulline / Q000378:metabolism; D016207:Cytokines; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014508:Urea / Q000096:biosynthesis
D001688:Biological Products; D016207:Cytokines; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D014508:Urea; D001120:Arginine