PMID- 9262374
OWN - NLM
STAT- MEDLINE
DCOM- 19970911
LR  - 20171116
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 282
IP  - 2
DP  - 1997 Aug
TI  - Interaction of ethanol with inducible nitric oxide synthase messenger RNA and 
      protein: direct effects on autacoids and endotoxin in vivo.
PG  - 1044-54
AB  - Inducible nitric oxide synthase (iNOS) mRNA is up-regulated in vivo by 
      dibutyryl-cAMP (db-cAMP), the purine-2y receptor agonist 2-methylthio-ATP and 
      Escherichia coli endotoxin lipopolysaccharide (LPS). Ethanol and 
      diethyldithiocarbamate inhibit LPS-stimulated iNOS mRNA. Their effects on 
      db-cAMP- and 2-methylthio-ATP-stimulated iNOS mRNA remain undefined. We examined 
      the effect of ethanol (4.5 g/kg intraperitoneal) and intratracheal 
      diethyldithiocarbamate (5 mg/kg) on intratracheal LPS (0.6 mg/kg), db-cAMP (0.1 
      and 1 mg/kg) or 2-methylthio-ATP (5 mg/kg)-stimulated rat alveolar macrophage 
      (AM) iNOS mRNA and protein, reactive nitrogen intermediates nitrite and nitrate 
      anion (RNI) and nuclear transcription factor-kappaB (NF-kappaB) in vivo. LPS and 
      the autacoids increased iNOS mRNA and protein in rat AM and RNI in 
      bronchoalveolar lavage fluid and in ex vivo incubates of AM compared with these 
      parameters in control rats (n = 6-21/group). Only LPS up-regulated TNF-alpha mRNA 
      and release of TNF-alpha in bronchoalveolar lavage fluid and AM. Ethanol 
      inhibited LPS stimulation of the iNOS cascade at the level of transcription but 
      inhibited only autacoid-stimulated iNOS protein and RNI. Diethyldithiocarbamate 
      selectively inhibited the LPS-stimulated iNOS cascade at the level of 
      transcription. Coadministration of ethanol and diethyldithiocarbamate inhibited 
      LPS-stimulated iNOS mRNA, protein and RNI more than either inhibitor alone but 
      did not differ from ethanol alone on autacoid-stimulated iNOS protein or RNI. LPS 
      increased and db-cAMP did not affect NF-kappaB in AM. Ethanol inhibited 
      LPS-stimulated NF-kappaB. Thus, two distinct pathways exist for induction of iNOS 
      mRNA in rat AM in vivo: an NF-kappaB pathway for LPS and cytokines inhibitable by 
      ethanol and diethyldithiocarbamate and an NF-kappaB-independent pathway, 
      refractory to inhibition by ethanol and diethyldithiocarbamate for db-cAMP and 
      2-mes-ATP. Finally, ethanol inhibits iNOS at the level of transcription and at 
      the level of the enzyme.
FAU - Greenberg, S S
AU  - Greenberg SS
AD  - Department of Medicine, The LSUMC Cardiovascular Center of Excellence, Louisiana 
      State University Medical Center, New Orleans, USA.
FAU - Ouyang, J
AU  - Ouyang J
FAU - Zhao, X
AU  - Zhao X
FAU - Xie, J
AU  - Xie J
FAU - Wang, J F
AU  - Wang JF
FAU - Giles, T D
AU  - Giles TD
LA  - eng
GR  - NIAAA 09816/AA/NIAAA NIH HHS/United States
GR  - NIAAA 1P50-AA09803/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Autacoids)
RN  - 0 (Endotoxins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thionucleotides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3K9958V90M (Ethanol)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 99Z2744345 (Ditiocarb)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - Y37441OBL1 (2-methylthio-ATP)
SB  - IM
MH  - Adenosine Triphosphate/analogs & derivatives/pharmacology
MH  - Animals
MH  - Autacoids/*metabolism
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Bucladesine/pharmacology
MH  - Ditiocarb/pharmacology
MH  - Endotoxins/*metabolism
MH  - Enzyme Induction
MH  - Ethanol/blood/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages, Alveolar/drug effects/enzymology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Synthase/biosynthesis/*genetics
MH  - RNA, Messenger/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thionucleotides/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation/drug effects
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1997 Aug;282(2):1044-54.