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2017 ; 21
(11
): 2926-2936
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gab.com Text
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English Wikipedia
Cimifugin suppresses allergic inflammation by reducing epithelial derived
initiative key factors via regulating tight junctions
#MMPMID28597545
Wang X
; Jiang X
; Yu X
; Liu H
; Tao Y
; Jiang G
; Hong M
J Cell Mol Med
2017[Nov]; 21
(11
): 2926-2936
PMID28597545
show ga
Cimifugin is a bioactive component of Saposhnikovia divaricata, a Chinese herb
for treating allergy. Our previous studies demonstrated that cimifugin inhibited
allergic inflammation efficiently. This study aims to determine the mechanism of
cimifugin on epithelial cells in allergic inflammation. Mice were sensitized and
challenged with FITC to establish type 2 atopic dermatitis (AD) model. The
initial stage of AD model, in which mice were just sensitized with FITC, was
established in vivo and immortalized human epidermal (HaCaT) cells were utilized
in vitro. Initiative key cytokines, TSLP and IL-33, were measured by ELISA, the
junctions in ECs were observed by electron microscopy and TJs (CLDN-1, occludin
and CLDND1) were assessed by Western blot, immunohistochemistry and
immunofluorescence. The results showed that TSLP and IL-33 were inhibited
significantly by cimifugin in the initial stage of AD model. Simultaneously,
cimifugin reduced the separated gap among the epithelial cells and increased the
expression of TJs. Similar effects on TSLP/IL-33 and TJs were obtained in vitro.
The effect of cimifugin on TSLP decreased significantly when expression of CLDN1
was interfered with siRNA and this implied cimifugin inhibits initiative
cytokines through restoring TJs. Furthermore, cimifugin administered only in the
initial stage obviously attenuated the ultimate allergic inflammation, which
indicate that impacts of cimifugin in the initial stage on TSLP/IL-33 and TJs are
sufficient for suppressing allergic inflammation. This study not only revealed
the mechanisms of cimifugin, but also indicated the possibility of initiative key
cytokines and TJs as therapeutic targets.