Overlapping gene expression profiles in rheumatoid fibroblast-like synoviocytes induced by the proinflammatory cytokines interleukin-1 beta and tumor necrosis factor.
OBJECTIVE
The development of therapies directed against TNF alpha and IL-1 beta 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 alpha and IL-1 beta.


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 alpha and IL-1 beta. 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 alpha and 2.4% for IL-1 beta), 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 alpha and IL-1 beta, reflecting the distal signaling pathways shared by these cytokines. A large number of novel TNF alpha and IL-1 beta-regulated genes were identified.


CONCLUSIONS
A panel of novel TNF alpha- and IL-1 beta-regulated genes was identified, and these are promising candidates for further study in relation to RA and other inflammatory diseases.
Taberner
M
M
Arthritis and Inflammation Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW, 2010, Australia.
Scott
K F
KF
Weininger
L
L
Mackay
C R
CR
Rolph
M S
MS
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha