Diethyldithiocarbamate inhibits induction of macrophage NO synthase.
We investigated whether sodium diethyldithiocarbamate (DETC), an inhibitor of the nuclear transcription factor kappa B (NFkappa B), modulates induction of NO synthase (NOS) in murine bone marrow-derived macrophages. A short exposure (between 1 and 16 h) of L929-cell medium-preconditioned macrophages to E. coli lipopolysaccharide (LPS) significantly increased the level of NOS mRNA, and elicited NO formation as detected by electron spin resonance spectroscopy and by the release of nitrite. DETC (0.1-1 mM) present during stimulation with LPS prevented the increase in NOS mRNA and the expression of NOS activity. These findings suggest that NFkappa B is involved in the signal transduction pathway linking stimulation of macrophages by LPS with transcription of the gene encoding inducible NOS.
Mülsch
A
A
Department of Applied Physiology, University of Freiburg, Germany.
Schray-Utz
B
B
Mordvintcev
P I
PI
Hauschildt
S
S
Busse
R
R
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015342:DNA Probes; D004050:Ditiocarb / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D007739:L Cells; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D017077:Culture Media, Conditioned; D015342:DNA Probes; D016328:NF-kappa B; D009573:Nitrites; D012333:RNA, Messenger; D004050:Ditiocarb; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases