Linked Life Data

14703771

Source:http://linkedlifedata.com/resource/pubmed/id/14703771

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-1-5
pubmed:abstractText
Lung fibrosis is the end-point of numerous lung disorders induced by a pneumonia or by a variety of different noxes, one of which is the cytostatic drug bleomycin (BLM). Fibrosis is characterized by excessive extracellular matrix accumulation. Macrophage-fibroblast interactions are suggested to play an important role in the development of this disease. The present study was addressed to investigate one possible pathway of this interaction, the influence of soluble mediators produced by BLM-stimulated macrophages on lung fibroblast collagen synthesis and modification. Conditioned media (CM) of BLM-exposed macrophages of the cell line NR8383 submitted to rat lung fibroblast cultures increased the activity of prolyl 4-hydroxylase (P4H) in fibroblasts in a dose dependent manner. CM of stimulated macrophages increased the collagen concentration in fibroblast culture supernatant. The level of mRNAs specific for the alpha-subunit of P4H and that for alpha1(I) collagen were found to be increased by about two-fold, that for lysyloxidase (LO) by about 2.5-fold in fibroblasts cultured in CM of stimulated macrophages. Pre-incubation of CM of BLM-exposed macrophages with neutralizing antibodies against TGF-beta or against PDGF resulted in a partial reversal of the increasing effect of the CM on P4H- and LO-activities in fibroblasts. Both growth factors, TGF-beta and PDGF, added to fibroblast cultures led to significant increases of P4H activity in the treated cells. We conclude that TGF-beta and PDGF produced by stimulated macrophages are involved in the regulation of the expression of alpha1(I) collagen, of P4H-alpha-subunit and LO in lung fibroblasts. The results indicate that this is not a direct effect but involves the action of a so far unidentified mediator responsible for autocrine stimulation of collagen production.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0940-2993
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14703771-Animals, pubmed-meshheading:14703771-Antibodies, Blocking, pubmed-meshheading:14703771-Bleomycin, pubmed-meshheading:14703771-Cells, Cultured, pubmed-meshheading:14703771-Collagen Type I, pubmed-meshheading:14703771-Culture Media, Conditioned, pubmed-meshheading:14703771-Dose-Response Relationship, Drug, pubmed-meshheading:14703771-Female, pubmed-meshheading:14703771-Fibroblasts, pubmed-meshheading:14703771-Gene Expression Regulation, pubmed-meshheading:14703771-Macrophages, pubmed-meshheading:14703771-Platelet-Derived Growth Factor, pubmed-meshheading:14703771-Procollagen-Proline Dioxygenase, pubmed-meshheading:14703771-Protein-Lysine 6-Oxidase, pubmed-meshheading:14703771-RNA, Messenger, pubmed-meshheading:14703771-Rats, pubmed-meshheading:14703771-Rats, Inbred WKY, pubmed-meshheading:14703771-Transforming Growth Factor beta
pubmed:year
2003
pubmed:articleTitle
Evidence for the involvement of TGF-beta and PDGF in the regulation of prolyl 4-hydroxylase and lysyloxidase in cultured rat lung fibroblasts.
pubmed:affiliation
Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany. koslowsk@rcs.urz.tu-dresden.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't