Overlapping gene expression profiles in rheumatoid fibroblast-like synoviocytes induced by the proinflammatory cytokines interleukin-1 β and tumor necrosis factor

Abstract.

Objective and Design: The development of therapies directed against TNF α and IL-1 β has underscored the importance of these cytokines in rheumatoid arthritis (RA). In this study, oligonucleotide microarrays were used to identify novel transcriptional events mediated by TNF α and IL-1 β.

Methods: In this study we have used Affymetrix U95A GeneChips representing 12,600 full-length human genes to identify transcriptional events mediated by these cytokines. Fibroblast-like synoviocytes were cultured from rheumatoid synovium from RA patients and stimulated with TNF α and IL-1 β. Gene transcript levels were determined using Affymetrix U95A GeneChips representing 12,600 full-length human genes.

Results: A large number of differentially regulated genes were identified (1.7% of array-displayed genes for TNF α and 2.4% for IL-1 β), and the validity of the array protocol was subsequently confirmed using real-time PCR. The majority of the differentially expressed genes were regulated by both TNF α and IL-1 β, reflecting the distal signaling pathways shared by these cytokines. A large number of novel TNF α and IL-1 β-regulated genes were identified.

Conclusions: A panel of novel TNF α- and IL-1 β-regulated genes was identified, and these are promising candidates for further study in relation to RA and other inflammatory diseases.