Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-11-17
pubmed:abstractText
To study the role of tumor necrosis factor-alpha (TNF-alpha) in fibrotic lung repair, we evaluated changes in lung TNF-alpha content and binding during the evolution of the fibrotic response. We concomitantly examined the effect of TNF-alpha on lung fibroproliferative responses. Lung TNF-alpha increased early after injury, at a time when lung tissue and lung fibroblasts exhibited increased binding to the cytokine. Fibroblasts isolated during this phase, which have increased spontaneous proliferative activity, had significant reduction in DNA synthesis when exposed to TNF-alpha. In contrast, DNA synthesis in normal and repair phase fibroblasts was inhibited by TNF-alpha. We also examined mechanisms of transduction of the TNF-alpha fibroproliferative signal, and observed that phosphorylating enzymes and G-proteins were involved. We conclude that TNF-alpha has a dual role in fibrotic repair. During injury, when uncontrolled fibroblast proliferation occurs, TNF-alpha production is increased to slow down the fibroproliferative response. During repair, when fibroblasts participate in structural restitution, TNF-alpha plays a salutary role by stimulating cellular proliferation. These effects of TNF-alpha on cellular proliferation are mediated by activation of two separate signal transduction pathways, phosphorylating enzymes and G-proteins. The observed variability in the effect of TNF-alpha may be related to changes in the phenotypic and genotypic characteristics of repairing lung fibroblasts which alter their responsiveness to exogenous stimuli.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1078-0297
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Role of tumor necrosis factor-alpha in regulating fibrotic lung repair.
pubmed:affiliation
John D Dingell VAMC, and Division of Pulmonary and Critical Care Medicine, Wayne State University School of Medicine, Detroit, MI, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't