METABOLISM OF AGMATINE IN MACROPHAGES - MODULATION BY LIPOPOLYSACCHARIDE AND INHIBITORY CYTOKINES

Agmatine is an amine derived from the decarboxylation of arginine by a rginine decarboxylase (ADC) and metabolized to putrescine by agmatinas e. While prevalent in bacteria and plants, agmatine and its metabolic enzymes have been recently identified in mammalian tissues. In the pre sent study we sought to determine: (a) whether macrophages (cell line RAW 264.7) express ADC and agmatinase, and (b) if the enzymes are regu lated by lipopolysaccharide (LPS), and/or by the inhibitory cytokines transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10) and interleukin-4 (IL-4). LPS induced a dose-dependent stimulation of agm atinase, while it decreased ADC, the effect in both cases being maximu m at 20 h. As expected, LPS dose-dependently stimulated the inducible nitric oxide synthase activity (iNOS). A strong correlation was observ ed between the effects of LPS on the agmatine-related enzymes and iNOS . By contrast, exposure to IL-10 and TGF-beta caused a reduction in AD C and agmatinase, whereas IL-4 was ineffective on ADC, but reverted th e LPS-induced increase of agmatinase. We conclude that the agmatine pa thway may be an alternative metabolic route for arginine in macrophage s, suggesting a regulatory role of agmatine during inflammation.