Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-2-19
pubmed:abstractText
IL-1 is important in regulating lung inflammation and potentially fibrosis as well. To clarify the role of this cytokine vis-à-vis changes in lung fibroblast phenotype in pulmonary fibrosis, the effects of IL-1beta on isolated lung fibroblasts were examined. Rat lung fibroblasts were treated with increasing doses of IL-1beta and examined for effects on cell number, alpha-smooth muscle actin expression, apoptosis, nitric oxide (NO) production, and contractility in collagen gels. The results show that IL-1beta caused dose-dependent down-regulation of alpha-smooth muscle actin protein and mRNA expression. The kinetics of mRNA inhibition was rapid and preceded the effects on protein expression. This IL-1beta-induced decrease in actin expression was associated with inhibition of contractility evaluated using fibroblast-populated collagen gels. Since IL-1beta inhibition of actin expression was accompanied by reduction in cell number, the effect on apoptosis was examined. Significant increase in the number of apoptotic nuclei and DNA fragmentation was observed upon IL-1beta treatment, with a dose-response curve that mirrored that for the decline in actin-positive cells. More than one-half of the apoptotic cells were actin positive at high IL-1beta doses, suggesting that the actin-expressing cells may be more susceptible to IL-1beta-induced apoptosis. IL-1beta also induced NO production in these cells, which was inhibited by NG-monomethyl-L-arginine. Similarly, IL-1beta-induced apoptosis and inhibition of actin expression were inhibited by this arginine analogue. Hence, induction of apoptosis by IL-1beta via NO production may be an important mechanism for regulating lung fibroblast alpha-smooth muscle actin expression, and consequently its contractile phenotype as well.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1392-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Regulation of lung fibroblast alpha-smooth muscle actin expression, contractile phenotype, and apoptosis by IL-1beta.
pubmed:affiliation
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.