Open AccessCimifugin suppresses allergic inflammation by reducing epithelial derived initiative key factors via regulating tight junctions
Author(s) -
Wang Xiaoyu,
Jiang Xiaoyan,
Yu Xi,
Liu Hailiang,
Tao Yu,
Jiang Guorong,
Hong Min
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13204
Subject(s) - thymic stromal lymphopoietin , allergic inflammation , hacat , occludin , inflammation , tight junction , immunology , western blot , in vivo , proinflammatory cytokine , in vitro , chemistry , medicine , microbiology and biotechnology , biology , biochemistry , gene
Abstract 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 EC s were observed by electron microscopy and TJ s ( CLDN ‐1, occludin and CLDND 1) 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 TJ s. Similar effects on TSLP / IL ‐33 and TJ s were obtained in vitro . The effect of cimifugin on TSLP decreased significantly when expression of CLDN 1 was interfered with si RNA and this implied cimifugin inhibits initiative cytokines through restoring TJ s. 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 TJ s 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 TJ s as therapeutic targets.