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2015 ; 6
(11
): e1993
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A novel cyclic helix B peptide inhibits dendritic cell maturation during
amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1
#MMPMID26610206
Yang C
; Zhang Y
; Wang J
; Li L
; Wang L
; Hu M
; Xu M
; Long Y
; Rong R
; Zhu T
Cell Death Dis
2015[Nov]; 6
(11
): e1993
PMID26610206
show ga
We recently synthesized a novel proteolysis-resistant cyclic helix B peptide
(CHBP) that exhibits promising renoprotective effects. Dendritic cells (DCs) play
an activation role in acute rejection (AR). Thus, the present study was designed
to investigate the effects of CHBP on DCs in a rat renal transplantation model.
The left kidney was harvested from male Lewis rats and then transplanted into
male Wistar rats with or without CHBP treatment. Five successive treatment doses
of CHBP after transplantation significantly ameliorated AR with lower
histological injury, apoptosis and CD4(+) and CD8(+) T-cell infiltration in renal
allografts. CHBP reduced IFN-? and IL-1? levels but increased IL-4 and IL-10
levels in the serum. The number of mature DCs was significantly decreased in
renal allografts treated with CHBP. In addition, incubating DCs with CHBP in
vitro led to reduction in TNF-?, IFN-?, IL-1? and IL-12 levels and increase of
IL-10 expression at the protein level in the supernatant. Mechanistically, CHBP
inhibited TLR activation-induced DC maturation by increasing SOCS1 expression
through Jak-2/STAT3 signaling. In conclusion, CHBP suppresses renal allograft AR
by inhibiting the maturation of DCs via Jak-2/STAT3/SOCS1 signaling, suggesting
that CHBP may be an potential therapeutic drug for treating renal AR.