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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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The effect of Blimp-1 inhibition on the expression of BCMA, XBP-1, J-chain, and C-myc. Western blot and RT-PCR were performed 3 weeks after administration of the lentivirus Blimp-1 siRNA (study group) or PLL3.7 (control group). (A) Peripheral blood of the mice (8 mice per group) was collected, and mRNA expression of Blimp-1, BCMA, XBP-1, J-chain, and C-myc were detected by RT-PCR. (B) Spleen cells of mice were collected, and protein expression of XBP-1 and C-myc were detected by Western blot. Similar results were obtained from three individual experiments. C: control group, S: study group.
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Figure 5: The effect of Blimp-1 inhibition on the expression of BCMA, XBP-1, J-chain, and C-myc. Western blot and RT-PCR were performed 3 weeks after administration of the lentivirus Blimp-1 siRNA (study group) or PLL3.7 (control group). (A) Peripheral blood of the mice (8 mice per group) was collected, and mRNA expression of Blimp-1, BCMA, XBP-1, J-chain, and C-myc were detected by RT-PCR. (B) Spleen cells of mice were collected, and protein expression of XBP-1 and C-myc were detected by Western blot. Similar results were obtained from three individual experiments. C: control group, S: study group.

Mentions: The level of anti-dsDNA Abs in serum of MRL-Fas(lpr) mice was analyzed every 3 weeks to explore whether Blimp-1 could affect the production of anti-dsDNA Ab. As shown in Figure 5, the level of anti-dsDNA Ab increased gradually with the age of mice. At 15 weeks of age, the study group was injected with Blimp-1 siRNA, and the control group was injected with pLL3.7 vector only. While the anti-dsDNA Ab level continued to increase in control group, the level of anti-dsDNA Ab in the study group remained unchanged. When mice were sacrificed at 18 weeks of age, the anti-dsDNA Ab level in the study group was significantly lower than that of the control group (pā€‰<ā€‰0.05, Figure 4). These results suggest that inhibition of endogenous Blimp-1 could prevent anti-dsDNA Ab production.


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 effect of Blimp-1 inhibition on the expression of BCMA, XBP-1, J-chain, and C-myc. Western blot and RT-PCR were performed 3 weeks after administration of the lentivirus Blimp-1 siRNA (study group) or PLL3.7 (control group). (A) Peripheral blood of the mice (8 mice per group) was collected, and mRNA expression of Blimp-1, BCMA, XBP-1, J-chain, and C-myc were detected by RT-PCR. (B) Spleen cells of mice were collected, and protein expression of XBP-1 and C-myc were detected by Western blot. Similar results were obtained from three individual experiments. C: control group, S: study group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: The effect of Blimp-1 inhibition on the expression of BCMA, XBP-1, J-chain, and C-myc. Western blot and RT-PCR were performed 3 weeks after administration of the lentivirus Blimp-1 siRNA (study group) or PLL3.7 (control group). (A) Peripheral blood of the mice (8 mice per group) was collected, and mRNA expression of Blimp-1, BCMA, XBP-1, J-chain, and C-myc were detected by RT-PCR. (B) Spleen cells of mice were collected, and protein expression of XBP-1 and C-myc were detected by Western blot. Similar results were obtained from three individual experiments. C: control group, S: study group.
Mentions: The level of anti-dsDNA Abs in serum of MRL-Fas(lpr) mice was analyzed every 3 weeks to explore whether Blimp-1 could affect the production of anti-dsDNA Ab. As shown in Figure 5, the level of anti-dsDNA Ab increased gradually with the age of mice. At 15 weeks of age, the study group was injected with Blimp-1 siRNA, and the control group was injected with pLL3.7 vector only. While the anti-dsDNA Ab level continued to increase in control group, the level of anti-dsDNA Ab in the study group remained unchanged. When mice were sacrificed at 18 weeks of age, the anti-dsDNA Ab level in the study group was significantly lower than that of the control group (pā€‰<ā€‰0.05, Figure 4). These results suggest that inhibition of endogenous Blimp-1 could prevent anti-dsDNA Ab production.

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