Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1994-7-13
pubmed:abstractText
TNF-alpha is a multifunctional cytokine that has been shown to activate a number of intracellular second messenger pathways. Recent studies demonstrate that the sphingomyelinase-ceramide pathway plays a potential role in the activation of nuclear factor-kappa B (NF-kappa B) by TNF-alpha. The following experiments both confirm that the addition of ceramide to cells can activate NF-kappa B and demonstrate that a 48-h pretreatment with phorbol 12-myristate (PMA) results in the loss of the ceramide-induced NF-kappa B response. In parallel experiments, in which SW480 cells were pretreated with PMA, TNF-alpha provided a signal resulting in the nuclear translocation of NF-kappa B that was similar to untreated cells. These data combined suggest that additional pathways exist that TNF-alpha can use for the activation of NF-kappa B. Supplementary data demonstrates that TNF-alpha, ceramide, and PMA activate a human cytomegalovirus-(HCMV) beta gal construct (promoter is responsive to NF-kappa B) that was stably transfected into the TNF receptor-bearing tumor cell line, SW480. PMA pretreatment of these cells resulted in a significant decrease in both the PMA and ceramide generated responses, 6% and 0% of controls, respectively. However, the response generated by TNF-alpha was not inhibited significantly (96% of control cells). This data suggests that although ceramide and 1,2-diacylglycerol (DAG) pathways may contribute to TNF-alpha activation of NF-kappa B, impedance of these pathways does not block TNF-alpha from activating NF-kappa B nor induction of the functional activation of the NF-kappa B responsive reporter construct, HCMV.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5877-82
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8207213-Animals, pubmed-meshheading:8207213-Base Sequence, pubmed-meshheading:8207213-Binding Sites, pubmed-meshheading:8207213-Cell Line, pubmed-meshheading:8207213-Ceramides, pubmed-meshheading:8207213-Consensus Sequence, pubmed-meshheading:8207213-Cytomegalovirus, pubmed-meshheading:8207213-DNA, pubmed-meshheading:8207213-Diglycerides, pubmed-meshheading:8207213-Humans, pubmed-meshheading:8207213-Molecular Sequence Data, pubmed-meshheading:8207213-NF-kappa B, pubmed-meshheading:8207213-Protein Binding, pubmed-meshheading:8207213-Protein Kinase C, pubmed-meshheading:8207213-Proto-Oncogene Proteins c-jun, pubmed-meshheading:8207213-Sphingomyelin Phosphodiesterase, pubmed-meshheading:8207213-Tetradecanoylphorbol Acetate, pubmed-meshheading:8207213-Tumor Necrosis Factor-alpha
pubmed:year
1994
pubmed:articleTitle
Inhibition of ceramide pathway does not affect ability of TNF-alpha to activate nuclear factor-kappa B.
pubmed:affiliation
Institute for Inflammation and Experimental Medicine, Miles Research Center, West Haven, CT 06516.
pubmed:publicationType
Journal Article