title: Inhibition of B lymphocyte-induced maturation protein-1 reduces the production of autoantibody and alleviates symptoms of systemic lupus erythematosus.
abstract: The B lymphocyte-induced maturation protein-1 (Blimp-1) is an important transcription factor for the maintenance of antigen-specific immune responses, and it is crucial in the development of systemic lupus erythematosus (SLE). This study aimed to investigate the role of Blimp-1 in the development of SLE and autoimmune-like symptoms. Lentivirus-mediated Blimp-1 siRNA was constructed and injected into MRL-Fas(lpr) lupus mice. The expression levels of Blimp-1, J-chain, C-myc, XBP-1 and BCMA in peripheral blood mononuclear cells (PMBCs) were determined by RT-PCR. Anti-dsDNA autoantibody levels were detected using ELISA. The expression levels of Blimp-1 in liver, kidney, spleen and lymph nodes of mice were also detected by Western blot. The 24-h urinary protein was monitored weekly. Our results demonstrated that in MRL-Fas(lpr) lupus mice, Blimp-1 was upregulated in PMBCs, liver, kidney, spleen and lymph nodes. Administration of Blimp-1 siRNA reduced the expression of Blimp-1 and the anti-dsDNA level by 78 and 28%, respectively, in the peripheral blood, and the expression of XBP-1, J-chain and BCMA was also decreased. Although the Blimp-1 level in liver showed no significant changes, the levels of Blimp-1 in kidney, spleen and lymph nodes were dramatically decreased by 95, 72 and 47%, respectively. Kidney diseases induced by SLE in lupus mice were mitigated, and urinary protein levels were significantly decreased. These results indicate that Blimp-1 plays an important role in promoting the progression of SLE. Therefore, Blimp-1 may provide a new therapeutic target in the treatment of SLE.
authors.affiliation: Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, The Third Military Medical University , Chongqing , China and.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Niu
authors.forename: Mingxu
authors.initials: M
authors.lastname: Zhang
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Shaoli
authors.initials: S
authors.lastname: Deng
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D007144:Immunoglobulin J-Chains / Q000235:genetics / Q000276:immunology; D007275:Injections, Intravenous; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016086:Lentivirus / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D000074462:Positive Regulatory Domain I-Binding Factor 1; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D000071717:X-Box Binding Protein 1
chemical_list: D001323:Autoantibodies; D053301:B-Cell Maturation Antigen; D004268:DNA-Binding Proteins; D007144:Immunoglobulin J-Chains; C489428:Myc protein, mouse; C513258:Prdm1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; C490176:Tnfrsf17 protein, mouse; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: Anti-dsDNA autoantibody, Blimp-1, siRNA, SLE, 24-h urinary protein