Abstract
Cumulative evidence suggest that B-lymphocytes play a role in the development of systemic lupus erythematosus (SLE). Thus, the therapeutic approach targeting specific B cells provides a promising way to treat SLE. Blimp-1 (B lymphocyte induced maturation protein), a transcriptional factor, controls the terminal differentiation of mature B cells to plasma cells. To explore the potential of Blimp-1 in the SLE development, we constructed the adenovirus encoding Blimp-1 siRNA, and injected it into BWF1 lupus mice. The results demonstrated that Blimp-1 siRNA decreased the Blimp-1 expression of B cells by regulating XBP-1 (X Box binding protein-1), BCMA (B-cell maturation antigen) expression through c-myc pathway. In addition, Blimp-1 siRNA eliminated anti-dsDNA antibody-producing plsma cells, reduced serum anti-dsDNA antibody levels and impeded the development of lupus. Therefore, our data provide the insight into the mechanism of Blimp-1 in SLE development and might represent a promising therapeutic strategy for autoantibody-mediated diseases.
Copyright © 2012. Published by Elsevier Inc.
MeSH terms
-
Animals
-
Antibodies, Antinuclear / immunology
-
Antibodies, Antinuclear / metabolism
-
B-Cell Maturation Antigen / immunology
-
B-Cell Maturation Antigen / metabolism
-
B-Lymphocytes / cytology
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism
-
Blotting, Western
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology*
-
DNA-Binding Proteins / immunology
-
DNA-Binding Proteins / metabolism
-
Female
-
Lupus Erythematosus, Systemic / genetics
-
Lupus Erythematosus, Systemic / immunology*
-
Lupus Erythematosus, Systemic / metabolism
-
Male
-
Mice
-
Mice, Inbred NZB
-
Mice, Inbred Strains
-
Plasma Cells / cytology
-
Plasma Cells / immunology
-
Plasma Cells / metabolism
-
Positive Regulatory Domain I-Binding Factor 1
-
Proto-Oncogene Proteins c-myc / immunology
-
Proto-Oncogene Proteins c-myc / metabolism
-
RNA Interference / immunology*
-
RNA, Small Interfering / genetics
-
RNA, Small Interfering / immunology
-
Regulatory Factor X Transcription Factors
-
Reverse Transcriptase Polymerase Chain Reaction
-
Survival Analysis
-
Transcription Factors / genetics
-
Transcription Factors / immunology*
-
Transcription Factors / metabolism
-
X-Box Binding Protein 1
Substances
-
Antibodies, Antinuclear
-
B-Cell Maturation Antigen
-
DNA-Binding Proteins
-
Myc protein, mouse
-
Prdm1 protein, mouse
-
Proto-Oncogene Proteins c-myc
-
RNA, Small Interfering
-
Regulatory Factor X Transcription Factors
-
Tnfrsf17 protein, mouse
-
Transcription Factors
-
X-Box Binding Protein 1
-
Xbp1 protein, mouse
-
Positive Regulatory Domain I-Binding Factor 1