Thromb Haemost 2003; 90(04): 688-697
DOI: 10.1160/TH03-04-0208
Wound Healing and Inflammation/Infection
Schattauer GmbH

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

Greg Parsonage*
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
,
Francesco Falciani*
2   Department of Biochemistry, Division of Biosciences, Birmingham University, Birmingham, UK
,
Angela Burman*
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
,
Andrew Filer
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
,
Ewan Ross
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
,
Margarita Bofill
3   Laboratori de Retrovirologia, Hospital Universitari Germans Tries I Pujol, Institució Catalana de Recerca i Pujo, Badalona, Spain
,
Stuart Martin
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
,
Mike Salmon
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
,
Christopher D. Buckley
1   MRC Centre for Immune Regulation, Division of Immunity and Infection, Division of Biosciences, Birmingham University, Birmingham, UK
› Author Affiliations
Financial support: This work was funded by the UK medical research council (MRC) and the arthritis research campaign (arc). Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.
Further Information

Publication History

Received 03 April 2003

Accepted after revision 21 July 2003

Publication Date:
05 December 2017 (online)

Summary

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, syn-ovial 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-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-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.

This publication was partially financed by Serono Foundation for the Advancement of Medical Science.

Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.

* The first three authors contributed equally to this work