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

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH03-04-0208
Issue: 2003: 90/4 (Oct) pp. 556-773
Pages: 688-697

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

Greg Parsonage (1) , Francesco Falciani (2) , Angela Burman (1) , Andrew Filer (1) , Ewan Ross (1) , Margarita Bofill (3) , Stuart Martin (1) , Mike Salmon (1) , Christopher D. Buckley (1)
(1) MRC Centre for Immune Regulation, Division of Immunity and Infection, and (2) Department of Biochemistry, Division of Biosciences, Birmingham University, Birmingham, UK (3) Laboratori de Retrovirologia, Hospital Universitari Germans Tries I Pujol, I

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 fibro-blasts to TNF-α ,IFN-γ and IL-4 stimulation were markedly dif-ferent, 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 rel-evant, 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 inflammato-ry cytokines that are characteristic of different tissues. Our data supports the concept that fibroblasts are hetero-geneous, 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.