Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils in vivo by endotoxin and its suppression by prednisolone.
Nitric oxide is believed to participate in nonspecific cellular immunity. Gram negative bacterial endotoxins increase the production of reactive nitrogen intermediates (RNI) in phagocytic cells by inducing the enzyme nitric oxide synthase II (NOS II). Anti-inflammatory glucocorticoids attenuate endotoxin-induced increases in RNI. This study evaluated the effect of in vivo administration of prednisolone on Escherichia coli lipopolysaccharide endotoxin (LPS)-induced increases in plasma RNI and neutrophil mRNA for NOS II and production of RNI in the rat. We show that LPS rapidly induces mRNA for NOS II and production of RNI (NO2- and NO3- anion) in rat neutrophils within 2 hr after in vivo administration of a sublethal dose of 0.5 mg/kg, i.v. A pharmacologic dose of prednisolone (50 micrograms/kg, im) given 15 min before LPS-attenuated production of NO2- and NO3- by neutrophils and suppressed LPS-stimulated mRNA for NOS II. 3-Amino, 1,2,4-triazine inhibited NO2- and NO3- production without affecting gene expression for NOS II. These data demonstrate that LPS rapidly induces functional gene expression for NOS II and prednisolone prevents induction of NOS II activity by inhibiting transcription of its mRNA.
Kolls
J
J
Department of Medicine, Physiology and Pharmacology, Louisiana State University Medical Center, New Orleans 70112.
Xie
J
J
LeBlanc
R
R
Malinski
T
T
Nelson
S
S
Summer
W
W
Greenberg
S S
SS
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology
D004731:Endotoxins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014227:Triazines; C085327:3-amino-1,2,4-triazine; D009569:Nitric Oxide; D011239:Prednisolone; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases