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Inhibition of B lymphocyte-induced maturation protein-1 reduces the production of autoantibody and alleviates symptoms of systemic lupus erythematosus.

Luo J, Niu X, Zhang M, Zhang K, Chen M, Deng S - Autoimmunity (2014)

Bottom Line: 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.These results indicate that Blimp-1 plays an important role in promoting the progression of SLE.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, The Third Military Medical University , Chongqing , China and.

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.

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Immunohistochemical staining of Blimp-1. C: control group, S: study group. The numbers of Blimp-1 positive cells (marked by black arrows) in glomerulus, renal tubular epithelium, spleen, and lymph nodes of the control group were obviously greater than those in the Blimp-1 siRNA-treated group. Blimp-1 expression of blood, kidney, spleen and lymph node was decreased significantly following Blimp-1 siRNA administration.
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Figure 3: Immunohistochemical staining of Blimp-1. C: control group, S: study group. The numbers of Blimp-1 positive cells (marked by black arrows) in glomerulus, renal tubular epithelium, spleen, and lymph nodes of the control group were obviously greater than those in the Blimp-1 siRNA-treated group. Blimp-1 expression of blood, kidney, spleen and lymph node was decreased significantly following Blimp-1 siRNA administration.

Mentions: To examine the impact of Blimp-1 siRNA on Blimp-1 expression in MRL-Fas(lpr) mice, the Blimp-1 mRNA and protein expression levels were determined by RT-PCR and Western blot, respectively. Blimp-1 was highly expressed in PMBCs (Figure 1), kidney, spleen, lymph nodes and liver of MRL-Fas(lpr) mice (Figure 2). Interestingly, after administration of Blimp-1 siRNA for 21 days, the expression level of Blimp-1 mRNA in PMBCs declined by 78% (Figure 1, right). No changes in Blimp-1 were detected in the liver; however, the Blimp-1 expression in kidney, spleen and lymph nodes declined by 95, 72 and 47%, respectively (Figure 2). The results of immunohistochemical staining indicated that Blimp-1-positive cells (brown color) were mainly distributed in glomerular mesangial cells and tubular epithelial cells, and the number of Blimp-1 positive cells in glomerulus, renal tubular epithelium, spleen and lymph nodes in the Blimp-1 siRNA-treated group were significantly reduced compared to those in the non-treated control group (Figure 3, pā€‰<ā€‰0.05), suggesting that the endogenous Blimp-1 level was significantly reduced following systemic injection of Blimp-1 siRNA.


Inhibition of B lymphocyte-induced maturation protein-1 reduces the production of autoantibody and alleviates symptoms of systemic lupus erythematosus.

Luo J, Niu X, Zhang M, Zhang K, Chen M, Deng S - Autoimmunity (2014)

Immunohistochemical staining of Blimp-1. C: control group, S: study group. The numbers of Blimp-1 positive cells (marked by black arrows) in glomerulus, renal tubular epithelium, spleen, and lymph nodes of the control group were obviously greater than those in the Blimp-1 siRNA-treated group. Blimp-1 expression of blood, kidney, spleen and lymph node was decreased significantly following Blimp-1 siRNA administration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389764&req=5

Figure 3: Immunohistochemical staining of Blimp-1. C: control group, S: study group. The numbers of Blimp-1 positive cells (marked by black arrows) in glomerulus, renal tubular epithelium, spleen, and lymph nodes of the control group were obviously greater than those in the Blimp-1 siRNA-treated group. Blimp-1 expression of blood, kidney, spleen and lymph node was decreased significantly following Blimp-1 siRNA administration.
Mentions: To examine the impact of Blimp-1 siRNA on Blimp-1 expression in MRL-Fas(lpr) mice, the Blimp-1 mRNA and protein expression levels were determined by RT-PCR and Western blot, respectively. Blimp-1 was highly expressed in PMBCs (Figure 1), kidney, spleen, lymph nodes and liver of MRL-Fas(lpr) mice (Figure 2). Interestingly, after administration of Blimp-1 siRNA for 21 days, the expression level of Blimp-1 mRNA in PMBCs declined by 78% (Figure 1, right). No changes in Blimp-1 were detected in the liver; however, the Blimp-1 expression in kidney, spleen and lymph nodes declined by 95, 72 and 47%, respectively (Figure 2). The results of immunohistochemical staining indicated that Blimp-1-positive cells (brown color) were mainly distributed in glomerular mesangial cells and tubular epithelial cells, and the number of Blimp-1 positive cells in glomerulus, renal tubular epithelium, spleen and lymph nodes in the Blimp-1 siRNA-treated group were significantly reduced compared to those in the non-treated control group (Figure 3, pā€‰<ā€‰0.05), suggesting that the endogenous Blimp-1 level was significantly reduced following systemic injection of Blimp-1 siRNA.

Bottom Line: 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.These results indicate that Blimp-1 plays an important role in promoting the progression of SLE.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, The Third Military Medical University , Chongqing , China and.

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.

Show MeSH
Related in: MedlinePlus