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Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by
Dendritic-cell-based functional screening
#MMPMID28272439
Chen S
; Zhou J
; Cai Y
; Zheng X
; Xie S
; Liao Y
; Zhu Y
; Qin C
; Lai W
; Yang C
; Xie X
; Du C
Sci Rep
2017[Mar]; 7
(?): 43820
PMID28272439
show ga
Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune
diseases including multiple sclerosis, and targeting DCs' cytokines production is
an important strategy for autoimmune diseases treatment. By establishing a
high-throughput screening system, we analyzed LOPAC drug library to identify
drugs that control the secretion of IL-6 by DCs, we selected the most likely
candidate drug, BVDU, and found that it affected not only IL-6 production, but
also that of IL-12, IL-1? during the DCs differentiation and maturation. The
mechanism studies showed that BVDU treatment restricted the phosphorylation of
MAP kinase, which played an important role in DC cytokine production. We further
assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE
and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly
lower EAE clinical scores, decreased leukocyte infiltration in central nervous
system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also
showed promising therapeutic effects based on both alleviated disease symptoms
and tissue pathogenesis. More interestingly, the modulating effect of BVDU on
IL-6 production was further verified in human primary DCs. The above data
supported the promising application of our screen model, and also the potential
of BVDU for autoimmune diseases therapy.
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