PMID- 9835279
OWN - NLM
STAT- MEDLINE
DCOM- 19990222
LR  - 20171116
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 22
IP  - 8
DP  - 1998 Nov
TI  - Ethanol inhibits the potentiation of endotoxin by dibutyryl cAMP and 2-methylthio 
      ATP in vivo.
PG  - 1662-72
AB  - Ethanol (ETOH) selectively suppressed Escherichia coli endotoxin 
      lipopolysaccharide (LPS)-stimulated, but not dibutyryl cAMP (db-cAMP)-stimulated 
      upregulation of inducible nitric oxide synthase (iNOS) in rat alveolar 
      macrophages (AMs) in vivo (Zhao et al., Alcohol. Clin. Exp. Res. 21:1062-1074, 
      1997). LPS-induced stimulation of iNOS is inhibited in vitro by db-cAMP and 
      purine-2-Y (P2Y) receptor-mediated agonists. We examined the effect of ETOH on 
      this interaction in rat lung AMs in vivo. Two hours after co-administration of 
      LPS [0.6 mg/kg, intratracheal (i.t.)] with db-cAMP (0.1 mg/kg, i.t.) or 
      2-methylthio-adenosine-triphosphate (2-mes-ATP) to Sprague-Dawley rats (225 to 
      250 g) (n = 10 to 24/gp) iNOS messenger ribonucleic acid (mRNA), iNOS protein, 
      and nitrate and nitrite anions [reactive nitrogen intermediates (RNIs)] in 
      bronchoalveolar lavage fluid (BALf), and the ex vivo incubates of AMs were 
      increased more than when these compounds were given individually to the rats. 
      Co-administration of LPS with the autacoids did not affect LPS-stimulated 
      increases of tumor necrosis factor-alpha (TNF alpha) mRNA, but inhibited 
      LPS-stimulated BALf TNF alpha protein and attenuated LPS-mediated decreases of 
      cell-associated TNF alpha. Pretreatment of rats with ETOH (4.5 g/kg, i.p.) or 
      diethyidithiocarbamate (DETC; 5 mg/kg, i.t.), an inhibitor of the nuclear 
      transcription factor NF kappa B (NF-kappaB), 30 min before co-administration of 
      LPS with the autacoids restored iNOS mRNA levels to that obtained with the 
      autacoid alone. Pretreatment of rats with ETOH decreased iNOS protein and RNI 
      below that produced by either compound given individually to the rats. Although 
      pretreatment of rats with DETC also decreased iNOS protein and RNI levels 
      produced by LPS, the levels of both substances were elevated above that of the 
      autacoid alone, LPS-induced upregulation of iNOS mRNA was associated with 
      elevated levels of p65/p50 NF-kappaB in the nucleus of AMs. Neither db-cAMP or 
      2-mes-ATP affected LPS-stimulated NF-kappaB-DNA binding. Moreover, ETOH and DETC 
      inhibited LPS-stimulated NF-kappaB-DNA binding. We conclude that in rat AMs in 
      vivo: (1) both db-cAMP and P2Y-receptor stimulation summate with, rather than 
      inhibit, LPS-induced upregulation of the iNOS mRNA, protein, and RNI; (2) ETOH 
      and DETC inhibit LPS-induced upregulation of iNOS mRNA only when stimulated 
      through the NF-kappaB pathway; and (3) ETOH inhibits both autacoid and 
      LPS-stimulated formation of iNOS protein by a mechanism independent of its 
      ability to suppress iNOS transcription.
FAU - Zhao, X
AU  - Zhao X
AD  - Department of Medicine, The Alcohol Research Center, Louisiana State University 
      Medical Center, New Orleans 70112, USA.
FAU - Jie, O
AU  - Jie O
FAU - Li, H
AU  - Li H
FAU - Xie, J
AU  - Xie J
FAU - Greenberg, S S
AU  - Greenberg SS
LA  - eng
GR  - 1P05-AA09803/AA/NIAAA NIH HHS/United States
GR  - R01-AA-09816/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thionucleotides)
RN  - 3K9958V90M (Ethanol)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
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  - Bucladesine/*pharmacology
MH  - Escherichia coli/*immunology
MH  - Ethanol/*pharmacology
MH  - Lipopolysaccharides/*immunology
MH  - Macrophages, Alveolar/*drug effects
MH  - Male
MH  - NF-kappa B/drug effects
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - RNA, Messenger/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thionucleotides/*pharmacology
MH  - Up-Regulation/drug effects
EDAT- 1998/12/03 00:00
MHDA- 1998/12/03 00:01
CRDT- 1998/12/03 00:00
PHST- 1998/12/03 00:00 [pubmed]
PHST- 1998/12/03 00:01 [medline]
PHST- 1998/12/03 00:00 [entrez]
AID - 00000374-199811000-00008 [pii]
PST - ppublish
SO  - Alcohol Clin Exp Res. 1998 Nov;22(8):1662-72.