Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-9-29
pubmed:abstractText
We investigated the extent to which fibroblasts isolated from diverse tissues differ in their capacity to modulate inflammation by comparing the global gene expression profiles of cultured human fibroblasts from skin, acute and chronically inflamed synovium, lymph node and tonsil. The responses of these fibroblasts to TNF-alpha, IFN-gamma and IL-4 stimulation were markedly different, as revealed by hierarchical cluster analysis and principal component analysis. In the absence of exogenous cytokine, synovial and skin fibroblasts exhibited similar patterns of gene expression. However their transcriptional profiles diverged upon treatment with TNF-alpha. This proved to be biologically relevant, as TNF-alpha induced the secretion of different patterns and amounts of IL-6, IL-8 and CCL2 (MCP-1) in the two fibroblast types. Co-culture of skin or synovial fibroblasts with synovial fluid-derived mononuclear cells provided further evidence that these transcriptional differences were functionally significant in an ex vivo setting. Interestingly, the transcriptional response of skin fibroblasts to IL-4 converged with that of TNF-alpha-treated synovial fibroblasts, suggesting resident tissue fibroblasts and their blood-borne precursors may be imprinted by inflammatory cytokines that are characteristic of different tissues. Our data supports the concept that fibroblasts are heterogeneous, and that they contribute to the tissue-specificity of inflammatory reactions. Fibroblasts are therefore likely to play an active role in the persistence of chronic inflammatory reactions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
688-97
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns.
pubmed:affiliation
MRC Centre for Immune Regulation, Division of Immunity and Infection, Birmingham University, Birmingham, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't