Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue levels distinct cytokine and chemokine expression patterns

Greg Parsonage, Francesco Falciani, Angela Burman, Andrew Filer, Ewan Ross, Margarita Bofill, Stuart Martin, Mike Salmon, Christopher D. Buckley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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-α, IFN-γ 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-α. This proved to be biologically relevant, as TNF-α induced the secretion of different patterns and amounts of IL-6, IL-8 and CCL2 (MCP-I) 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-α-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.

Original languageEnglish
Pages (from-to)688-697
Number of pages10
JournalThrombosis and Haemostasis
Issue number4
Publication statusPublished - 1 Oct 2003

Bibliographical note

Funding: This work was funded by the UK medical research council (MRC) and the arthritis research campaign (arc). This publication was partially financed by Serono Foundation for the Advancement of Medical Science.


  • Chemokine
  • Fibroblast
  • Human
  • Inflammation
  • Leucocyte


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