Olf1EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus 英文参考文献.docVIP

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Olf1EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus 英文参考文献.doc

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Olf1EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus 英文参考文献

Fengetal.ArthritisResearchTherapy2010,12:R59 /content/12/2/R59 RESEARCH ARTICLE OpenAccess Olf1/EBFassociatedzincfingerproteininterfered withantinuclearantibodyproductioninpatients withsystemiclupuserythematosus XuebingFeng1*?,RongliangLi1?,JingHuang1,HuayongZhang,LinaZhu1,BingzhuHua1,BettyPTsao2, LingyunSun1* Abstract Introduction:TheaimofthestudywastodeterminewhetherOlf1/EBFassociatedzincfingerprotein(OAZ),a transcriptionfactorencodedbyapositionalsystemiclupuserythematosus(SLE)candidategene,playsafunctional roleinthepathogenesisinSLE. Methods:Geneexpressionlevelsinperipheralbloodcells(PBLs)measuredusingquantitativereal-timepolymerase chainreaction(qPCR)wereassessedforassociationwithdiseaseactivityandthepresenceofspecific autoantibodies.Peripheralbloodmononuclearcells(PBMCs)wereincubatedwithspecificsiRNAsforthreedays, thencellswereharvestedformeasuringmRNAlevelsusingqPCR,andsupernatantsforlevelsoftotal immunoglobulin(Ig)GandIgMaswellassecretedcytokines,chemokineandantinuclearantibodies(ANA)using ELISA.IndirectimmunofluorescencewasalsoappliedforANAdetection. Results:OAZ gene expressions in PBLs from 40 ANA-positive SLE patients were significantly increased than those from 30 normal controls (P 0.0001) and 18 patients with rheumatoid arthritis (P 0.01). In SLE patients, OAZ transcripts were positively correlated with SLE disease activity index (SLEDAI) score (r = 0.72, P 0.0001) and higher in those positive for anti-dsDNA or anti-Sm antibodies (both P0.05). Co-culturing with OAZ siRNAs reduced mRNA levels of OAZ by 74.6 ±6.4% as compared to those co-cultured with non-targeting siRNA and OAZ silencing resulted in reduced total IgG, ANA, interferon (IFN)-g, interleukin (IL)-10, IL-12 and IL-21, but elevated CCL2 levels in culture supernatants (P 0.05). The declined ANA levels correlated with inhibited OAZ expression (r = 0.88, P = 0.05), reduced IL-21 levels (r = 0.99, P 0.01), and elevated chemokine (C-C motif) ligand 2levels (r = -0.98, P 0.01). Expressions of ID