Linked Life Data

17379849

Source:http://linkedlifedata.com/resource/pubmed/id/17379849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-6-18
pubmed:abstractText
Apoptosis of lung structural cells is crucial in the process of normal tissue repair. Insufficient apoptosis of lung fibroblasts may contribute to the development of fibrosis. Since the CC chemokine ligand 2 (CCL2) is associated with fibrotic disease and the cytokine IL-6 blocks apoptosis in many cell types, we hypothesized that CCL2 may contribute to the development of lung fibrosis by inducing IL-6, which, in turn, inhibits fibroblast apoptosis. Fibroblasts were cultured in the presence of CCL2, which stimulated IL-6 production and mRNA expression in a concentration-dependent manner (250-1,000 ng/ml). This effect was mediated through the ERK1/2 signaling pathway. In addition, through a feedback loop, the secreted IL-6 activated the fibroblasts as evidenced by immunoblotting for phosphorylated STAT3. CCL2 reduced fibroblast apoptosis induced by staurosporin as detected by DNA content profiling (53.6 +/- 10.8%, P < 0.05) and apoptosis induced by serum starvation as detected by COMET assay (Tail moment: 36.6 +/- 9.9 of control versus 3.6 +/- 1.4 of CCL2, P < 0.01). In the presence of anti-IL-6 neutralizing antibody, however, this anti-apoptotic effect of CCL2 was eliminated. These data suggest that CCL2 mediates fibroblast survival by inhibiting apoptosis through IL-6/STAT3 signaling and provides a novel mechanism through which CCL2 may contribute to the development and maintenance of lung fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The CC chemokine ligand 2 (CCL2) mediates fibroblast survival through IL-6.
pubmed:affiliation
University of Nebraska Medical Center, Department of Pulmonary and Critical Care Medicine, 985885 Nebraska Medical Center, Omaha, NE 68198-5885, USA.
pubmed:publicationType
Journal Article