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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Acta+Pharmacol+Sin
2015 ; 36
(11
): 1367-76
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Prednisone treatment inhibits the differentiation of B lymphocytes into plasma
cells in MRL/MpSlac-lpr mice
#MMPMID26456588
Yan SX
; Deng XM
; Wang QT
; Sun XJ
; Wei W
Acta Pharmacol Sin
2015[Nov]; 36
(11
): 1367-76
PMID26456588
show ga
AIM: A number of evidence shows that the differentiation of B lymphocytes into
plasma cells plays an important role in lupus pathogenesis. In this study we
investigated how prednisone, a classical therapeutic drug for autoimmune
diseases, regulated plasma cell differentiation in MRL/MpSlac-lpr mice. METHODS:
MRL/lpr mice were treated with prednisone (2.5 or 5 mg·kg(-1)·d(-1), ig) for 13
weeks, and the proteinuria levels and survival times were monitored. After the
mice were euthanized, blood sample, spleen and thymus were collected. The serum
levels of anti-dsDNA antibody, anti-nuclear antibody, IL-21, and IL-10 were
detected using ELISA kits. Subsets of splenic B and T lymphocytes were quantified
with flow cytometry. Transcription factor Blimp-1 and Bcl-6 expression was
determined using qPCR and Western blot. RESULTS: Prednisone treatment
dose-dependently attenuated the lupus symptoms in MRL/lpr mice with decreased
proteinuria levels, prolonged survival times, decreased serum anti-nuclear
antibody levels, and reduced spleen and thymus indices. Prednisone treatment also
significantly decreased the elevated percentages of plasma cells and plasma cell
precursors, decreased the percentages of activated T cells, and increased the
frequency of CD4(+)CD62L(+) cells, demonstrated that decreased anti-nuclear
antibodies and improvements in lupus symptoms were associated with decreased
plasma cells. Furthermore, prednisone treatment decreased serum IL-21 and IL-10
levels and reduced the expression of splenic Blimp-1 and Bcl-6 (two key
regulatory factors for plasma cell differentiation) in MRL/lpr mice. CONCLUSION:
Prednisone treatment restricts B lymphocyte differentiation into plasma cells in
MRL/lpr mice, which may be correlated with the inhibition of IL-21 production and
the restoration of the balance between Blimp-1 and Bcl-6.