Linked Life Data

9285487

Source:http://linkedlifedata.com/resource/pubmed/id/9285487

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1997-9-18
pubmed:abstractText
Lipopolysaccharide/interferon gamma up-regulated inducible nitric oxide synthase and caused nitric oxide generation and concomitant apoptotic cell death in RAW 264.7 macrophages. Exogenously supplied nitric oxide donors such as S-nitrosoglutathione produced equivalent alterations. Preactivation of macrophages with a combination of lipopolysaccharide/interferon gamma under conditions of blocked NO synthase--N(G)-monomethyl-L-arginine addition--or stimulation with a low, nondestructive dose of S-nitrosoglutathione conferred protection against high and thus apoptotic NO concentrations. Here we report that induction of cyclooxygenase-2 during the preactivation period is a critical regulator of macrophage apoptosis. Under resting conditions, macrophages do not express cyclooxygenase-2, whereas lipopolysaccharide/interferon gamma/N(G)-monomethyl-L-arginine prestimulation for 12-15 h caused protein expression. In parallel, preactivation of RAW cells with a low, nontoxic dose of S-nitrosoglutathione promoted protection and cyclooxygenase-2 up-regulation. To prove cyclooxygenase-2 involvement during protection, we stably transfected RAW 264.7 macrophages with a rat cyclooxygenase-2 expression vector. Cyclooxygenase-2 overexpressing macrophages, preactivated with the calcium liberating and thus phopholipase A2-activating agent A23187, revealed protection against exogenously supplied NO. Protection afforded by lipopolysaccharide/interferon gamma/N(G)-monomethyl-L-arginine prestimulation was completely reversed by the addition of the cyclooxygenase-2 selective inhibitor NS-398 or in macrophages stably transfected with an antisense cyclooxygenase-2 expression vector. Our results point to cyclooxygenase-2 induction by lipopolysaccharide/interferon gamma/N(G)-monomethyl-L-arginine or low-dose nitric oxide pretreatment conferring macrophage protection to the apoptotic action of nitric oxide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0892-6638
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
887-95
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Cyclooxygenase-2: an essential regulator of NO-mediated apoptosis.
pubmed:affiliation
University of Erlangen-Nürnberg, Faculty of Medicine, Department of Medicine IV-Experimental Division, Erlangen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't