Identification of Naf1/ABIN-1 among TNF-alpha-induced expressed genes in human synoviocytes using oligonucleotide microarrays.
The cytokine tumor necrosis factor alpha (TNF-alpha) is a critical effector of the pathogenesis of rheumatoid arthritis (RA). We used oligonucleotide microarray (OM) analysis to assess TNF-alpha-modulated gene expression in cultured primary human synoviocytes in vitro. Genes identified include cytokines and inflammatory mediators, extracellular matrix and adhesion molecules, cell cycle and proliferation related proteins, transcription related proteins, and apoptotic mediators. OM identified 1185 differentially expressed genes in TNF-alpha-treated synoviocytes. The regulation of Nef-associated factor-1 (Naf1), an A20-binding, nuclear factor kappa B (NFkappaB) inhibitory protein was probed further given its putative role as an endogenous brake for the expression of some TNF-alpha-driven genes. Naf1 mRNA levels were higher in synovial biopsies from patients with active RA and seronegative arthropathy than in those from patients with osteoarthritis. These findings underscore the value of transcriptome analysis in cytokine-activated synoviocyte cultures in vitro as a means of identifying disease-associated genes in human arthritis, and implicate Naf1 as a potential modulator of TNF-alpha bioactivity in RA.
Gallagher
Joanne
J
The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. joanne.gallagher@ucd.ie
Howlin
Jillian
J
McCarthy
Conor
C
Murphy
Evelyn P
EP
Bresnihan
Barry
B
FitzGerald
Oliver
O
Godson
Catherine
C
Brady
Hugh R
HR
Martin
Finian
F
D001168:Arthritis / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004268:DNA-Binding Proteins; C117046:TNIP1 protein, human; D014409:Tumor Necrosis Factor-alpha