Linked Life Data

12730147

Source:http://linkedlifedata.com/resource/pubmed/id/12730147

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-7-9
pubmed:abstractText
Although the mechanisms that underlie airway hyperresponsiveness in asthma are complex and involve a variety of factors, evidence now suggests that intrinsic abnormalities in airway smooth muscle (ASM) may play an important role. We previously reported that TNF-alpha, a cytokine involved in asthma, augments G-protein-coupled receptor (GPCR) agonist-evoked calcium responses in cultured ASM cells. Here we have extended our previous studies by investigating whether TNF-alpha also modulates the contractile and relaxant responses to GPCR activation using cultured murine tracheal rings. We found that in tracheal rings treated with 50 ng/ml TNF-alpha, carbachol-induced isometric force was significantly increased by 30% compared with those treated with diluent alone (P < 0.05). TNF-alpha also augmented KCl-induced force generation by 70% compared with rings treated with diluent alone (P < 0.01). The enhancing effect of TNF-alpha on carbachol-induced isometric force generation was completely abrogated in the tracheal rings obtained from TNF-alpha receptor (TNFR)1-deficient mice and in control rings treated with a TNF-alpha mutant that solely activates TNFR2. TNF-alpha also attenuated relaxation responsiveness to isoproterenol but not to PGE2 or forskolin. TNF-alpha modulatory effects on GPCR-induced ASM responsiveness were completely abrogated by pertussis toxin, an inhibitor of Gialpha proteins. Taken together, these data suggest that TNF-alpha may participate in the development of airway hyperresponsiveness in asthma via the modulation of ASM responsiveness to both contractile and beta-adrenoceptor GPCR agonists.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
8750-7587
pubmed:author
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
864-72; discussion 863
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12730147-Animals, pubmed-meshheading:12730147-Antigens, CD, pubmed-meshheading:12730147-Carbachol, pubmed-meshheading:12730147-Cholera Toxin, pubmed-meshheading:12730147-Dinoprostone, pubmed-meshheading:12730147-Drug Synergism, pubmed-meshheading:12730147-Female, pubmed-meshheading:12730147-Forskolin, pubmed-meshheading:12730147-Mice, pubmed-meshheading:12730147-Mice, Inbred BALB C, pubmed-meshheading:12730147-Muscle, Smooth, pubmed-meshheading:12730147-Muscle Contraction, pubmed-meshheading:12730147-Muscle Relaxation, pubmed-meshheading:12730147-Pertussis Toxin, pubmed-meshheading:12730147-Potassium Chloride, pubmed-meshheading:12730147-Receptors, G-Protein-Coupled, pubmed-meshheading:12730147-Receptors, Tumor Necrosis Factor, pubmed-meshheading:12730147-Receptors, Tumor Necrosis Factor, Type I, pubmed-meshheading:12730147-Trachea, pubmed-meshheading:12730147-Tumor Necrosis Factor-alpha
pubmed:year
2003
pubmed:articleTitle
TNF-[alpha] modulates murine tracheal rings responsiveness to G-protein-coupled receptor agonists and KCl.
pubmed:affiliation
Deparment of Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 1904, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't