title: Sirtuin 1 (Sirt1) Overexpression in BaF3 Cells Contributes to Cell Proliferation Promotion, Apoptosis Resistance and Pro-Inflammatory Cytokine Production.
abstract: BACKGROUND B lymphocyte hyperactivity is a main characteristic of systemic lupus erythematosus (SLE), and B lymphocytes play a prominent pathogenic role in the development and progression of SLE. The aim of this study was to investigate the role of Sirtuin 1 (Sirt1) in B lymphocytes. MATERIAL AND METHODS Mouse B lymphocytes BaF3 was transfected with Sirt1 vector or shRNA against Sirt1. Then the transfected cells viability and apoptosis were respectively determined by MTT assay and flow cytometry. In addition, the mRNA levels of three pro-inflammatory cytokines and p53 were detected by RT-PCR. Furthermore, the expression levels of nuclear factor-kappa B (NF-κB) pathway proteins were measured by Western blot. RESULTS Overexpression of Sirt1 significantly increased cell proliferation (p<0.05 or p<0.01) and significantly suppressed apoptosis (p<0.05). The mRNA level expressions of interleukin 1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) were significantly upregulated (p<0.05 or p<0.01), whereas p53 was significantly downregulated (p<0.05) by Sirt1 overexpression. In addition, the inhibitory subunit of NF-κB (IκBα) and p65 were significantly activated and phosphorylated (p<0.01 or p<0.001), and B-Cell CLL/Lymphoma 3 (Bcl-3) was significantly upregulated (p<0.05) by Sirt1 overexpression. CONCLUSIONS These results suggested that Sirt1 overexpression could promote BaF3 cell proliferation, inhibit apoptosis, and upregulate pro-inflammatory cytokines. The NF-κB pathway might be involved in these effects of Sirt1 on BaF3 cells, and Sirt1 might be a potential risk factor of SLE.
authors.affiliation: Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University (Qingdao Branch), Qingdao, Shandong, China (mainland).
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Xin
authors.affiliation: Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University (Qingdao Branch), Qingdao, Shandong, China (mainland).
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Mingshu
authors.initials: M
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D056564:Sirtuin 1