Inhibition of macrophage nitric oxide production by gangliosides derived from a spontaneous T cell lymphoma: the involved mechanisms.
Gangliosides (DLG) derived from a spontaneous T cell lymphoma (Dalton's lymphoma) have been shown to impair the ability of lipopolysaccharide-activated macrophages to produce nitric oxide (NO). However, the mechanism and nature of this effect is not known. In this investigation, we sought to (1) determine whether the inhibitory action of DLG on macrophages is through the modulation of inducible nitric oxide synthase (iNOS) expression and (2) identify the possible mechanisms and signal transduction events underlying the inhibitory action of DLG. Immunoblot analysis of DLG-treated macrophages showed a decrease in iNOS expression. DLG also inhibited the production of monokines interleukin-1 and tumor necrosis factor by macrophages. However, the DLG-induced inhibition was reversible in nature. Studies showed that DLG-induced inhibition of macrophage activation could be blocked by sodium orthovanadate, indicating a role of phosphatase activity in ganglioside-induced inhibition.
Bharti
Alok Chandra
AC
Cytokine Research Laboratory, Department of Bioimmunotherapy, Box 143, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. alokchandrab@yahoo.com
Singh
Sukh Mahendra
SM
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D005732:Gangliosides; D007375:Interleukin-1; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010744:Phosphoric Monoester Hydrolases