Gene expression profiling of S100 protein families in the peripheral blood from patients with RA, SLE, sJIA and polyJIA - correlation between S100A4 expression and joint destruction
Norihiro Nishimoto1, ○Hidehiko Sugino2(杉野英彦), Chieko Aoki1, Hooi-Ming Lee2, Kenichi Matsubara3 and Toru Mima1.
1Laboratory of Immune Regulation, Wakayama Medical University
2 Graduate School of Frontier Biosciences, Osaka University
3 DNA Chip Research Inc., Yokohama, Japan
Background: The S100 proteins are low molecular weight, acidic peptides of 10-12KD with two EF hand calcium binding domains. The S100 protein family is composed of at least 24 members in human and thought to be involved in cell proliferation and differentiation through regulating Calcium concentration. Recently, up-regulation of S100 calcium binding proteins in RA patients has been reported. Especially, S100A4, S100A8, S100A9 and S100A12 are more likely related to RA.
Objective: To know the pathological roles of S100 proteins families, we investigated the comprehensive gene expression profiling of seventeen S100 families using DNA microarray in patients with active rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polyarticular type juvenile idiopathic arthritis (polyJIA), and systemic-onset JIA (sJIA).
Methods: Total RNA was extracted from the peripheral blood obtained form 114 patients with RA, 12 patients with SLE, 6 patients with polyJIA, 51 patients with sJIA and 53 healthy individuals (45 adults and 8 children), and used to prepare amino allylRNA (aRNA). aRNA were subjected to Cy3 and Cy5 labeling and hybridized with an oligonucleotide-based DNA microarry. (AceGene Human 30K; DNA Chip Research Inc., Yokohama, Japan). The data among patients and healthy individuals were analyzed by parametric statistical group comparison.
Results: S100A4, A6, A8/9, A11 and A12 are significantly up-regulated in RA and polyJIA compared to healthy contorol. S100A6, A8/9, S100A11 and A12 were also up-regulated in SLE and sJIA. Interestingly, S100A4 was differentially increased in the groups of RA and polyJIA but not in the groups of SLE and sJIA. Except for these six S100A families, we investigated the expression levels of eleven S100 genes (S100A1, S100A2, S100A3, S100A5, S100A10, S100A13, S100A14, S100A16, S100B, S100G, and S100BP). Expression levels of these eleven S100 genes remained stationary among the RA, SLE, sJIA, polyJIA and healthy controls.
Conclusion: 1.The increased expressions of S100A4, A8/9 and A12 in the RA synovial tissue, synovial fluid and plasma have been previously reported from some groups, We confirmed the up-regulation of S100A4, S100A8/9 and S100A12 in RA. 2. We newly found the up-regulation of S100A6 and S100A11 in RA. 3. Furthermore, S100A4 was up-regulated in RA and poly JIA, but not in SLE and polyJIA, while S100A6, 100A8/9, S100A11, and S100A12 were commonly up-regulatied. Since RA and polyJIA show more serious joint destruction,100A4 may be an important factor of joint destruction in RA and polyJIA.