Linked Life Data

14734771

Source:http://linkedlifedata.com/resource/pubmed/id/14734771

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-1-21
pubmed:abstractText
The CD40-CD40 ligand (CD40L) system (CD154) is a central means of immune cell communication crucial for Ig class switching and enhanced Ag presentation. CD40 is also a key signaling conduit to activate nonhematopoietic cells, such as fibroblasts and endothelial cells, to produce proinflammatory mediators. Disruption of the CD40-CD40L pathway reduces lung inflammation and fibrosis, autoimmune disease and atherosclerosis. Non-bone marrow-derived structural cells are not known to express CD40L. In this study, we reveal the intriguing finding that primary strains of human lung fibroblasts derived from normal and scarred lung express both CD40L mRNA and protein. Interestingly, CD40L expression is down-regulated by IFN-gamma, a type 1 cytokine with antiscarring properties, and is up-regulated by the profibrogenic type 2 cytokine IL-13. Flow cytometry and laser confocal microscopy revealed that the majority of CD40L was located intracellularly. Importantly, fibroblast strains from human idiopathic pulmonary fibrosis tissue expressed increased levels of CD40L compared with fibroblasts from nonscarred lung. Fibroblasts in the scarred areas of human lung tissue expressed high levels of CD40L. Finally, the blood and lung lavage levels of CD40L are significantly elevated in fibrosis patients compared with normals. These new findings demonstrate that fibroblasts are a new source of CD40L and that those involved in scarring may have undergone a selected expansion for high CD40L expression. Moreover, the antifibrotic activity of IFN-gamma may involve the down-regulation of fibroblast CD40L levels. We speculate that fibroblast-derived CD40L plays a role in promoting fibroblast activation and possibly in interaction with CD40 bearing cells.
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
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1862-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Expression of CD154 (CD40 ligand) by human lung fibroblasts: differential regulation by IFN-gamma and IL-13, and implications for fibrosis.
pubmed:affiliation
Department of Microbiology and Immunology, Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't