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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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Related in: MedlinePlus

The renal pathological changes in the experimental groups. (a) capsular space; (b) endothelial cells; (c) lymphocytes; (d) capillary; (e) mesangial cells. In the control group, the numbers of glomerular mesangial and endothelial cells were increased compared to the study group, and glomerular capillary was dilated and congested with mild lymphocytic infiltration, which further narrowed the capsular space. After Blimp-1 expression was inhibited by Blimp-1 siRNA (study group), the glomerular pathological changes in the study group were mitigated. The numbers of mesangial and endothelial cells and the capsular space tended to be normal, and there were no significant inflammatory changes found in glomerulus.
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Figure 6: The renal pathological changes in the experimental groups. (a) capsular space; (b) endothelial cells; (c) lymphocytes; (d) capillary; (e) mesangial cells. In the control group, the numbers of glomerular mesangial and endothelial cells were increased compared to the study group, and glomerular capillary was dilated and congested with mild lymphocytic infiltration, which further narrowed the capsular space. After Blimp-1 expression was inhibited by Blimp-1 siRNA (study group), the glomerular pathological changes in the study group were mitigated. The numbers of mesangial and endothelial cells and the capsular space tended to be normal, and there were no significant inflammatory changes found in glomerulus.

Mentions: The renal pathological appearance was also examined. In the control group, the numbers of glomerular mesangial cells and endothelial cells were increased. In addition, the glomerular capillary was dilated and congested with mild lymphocytic infiltration, which further narrowed the capsular space. However, after Blimp-1 siRNA administration, the glomerular pathological changes were mitigated. In addition, the numbers of mesangial cells and endothelial cells as well as the capsular space were similar to those of normal controls, and no significant inflammatory changes were found in the glomerulus (Figure 6). These pathological results suggest that Blimp-1 siRNA can mitigate the renal inflammatory changes.


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)

The renal pathological changes in the experimental groups. (a) capsular space; (b) endothelial cells; (c) lymphocytes; (d) capillary; (e) mesangial cells. In the control group, the numbers of glomerular mesangial and endothelial cells were increased compared to the study group, and glomerular capillary was dilated and congested with mild lymphocytic infiltration, which further narrowed the capsular space. After Blimp-1 expression was inhibited by Blimp-1 siRNA (study group), the glomerular pathological changes in the study group were mitigated. The numbers of mesangial and endothelial cells and the capsular space tended to be normal, and there were no significant inflammatory changes found in glomerulus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: The renal pathological changes in the experimental groups. (a) capsular space; (b) endothelial cells; (c) lymphocytes; (d) capillary; (e) mesangial cells. In the control group, the numbers of glomerular mesangial and endothelial cells were increased compared to the study group, and glomerular capillary was dilated and congested with mild lymphocytic infiltration, which further narrowed the capsular space. After Blimp-1 expression was inhibited by Blimp-1 siRNA (study group), the glomerular pathological changes in the study group were mitigated. The numbers of mesangial and endothelial cells and the capsular space tended to be normal, and there were no significant inflammatory changes found in glomerulus.
Mentions: The renal pathological appearance was also examined. In the control group, the numbers of glomerular mesangial cells and endothelial cells were increased. In addition, the glomerular capillary was dilated and congested with mild lymphocytic infiltration, which further narrowed the capsular space. However, after Blimp-1 siRNA administration, the glomerular pathological changes were mitigated. In addition, the numbers of mesangial cells and endothelial cells as well as the capsular space were similar to those of normal controls, and no significant inflammatory changes were found in the glomerulus (Figure 6). These pathological results suggest that Blimp-1 siRNA can mitigate the renal inflammatory changes.

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