Premium
Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein‐coupled estrogen receptor: Probing a possible target for allergic inflammation
Author(s) -
Yuan WeiYuan,
Li LianQu,
Chen YanYan,
Zhou YiJing,
Bao KaiFan,
Zheng Jie,
Hua YongQing,
Jiang GuoRong,
Hong Min
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3hi0220-342rr
Subject(s) - gper , occludin , allergic inflammation , thymic stromal lymphopoietin , estrogen receptor , pharmacology , biology , inflammation , immunology , agonist , receptor , tight junction , microbiology and biotechnology , biochemistry , genetics , cancer , breast cancer
Allergic asthma is a common chronic lung inflammatory disease and seriously influences public health. We aim to investigate the effects of formononetin (FMN) and calycosin (CAL), 2 flavonoids in Radix Astragali , on allergic asthma and elucidate possible therapeutic targets. A house dust mite (HDM)‐induced allergic asthma mouse model and TNF‐α and Poly(I:C) co‐stimulated human bronchial epithelial cell line (16HBE) were performed respectively in vivo and in vitro. The role of G protein‐coupled estrogen receptor (GPER) was explored by its agonist, antagonist, or GPER small interfering RNA (siGPER). E‐cadherin, occludin, and GPER were detected by western blotting, immunohistochemistry, or immunofluorescence. The epithelial barrier integrity was assessed by trans‐epithelial electric resistance (TEER). Cytokines were examined by enzyme‐linked immunosorbent assay (ELISA). The results showed that flavonoids attenuated pulmonary inflammation and hyperresponsiveness in asthmatic mice. These flavonoids significantly inhibited thymic stromal lymphopoietin (TSLP), increased occludin and restored E‐cadherin in vivo and in vitro . The effects of flavonoids on occludin and TSLP were not interfered by ICI182780 (estrogen receptor antagonist), while blocked by G15 (GPER antagonist). Furthermore, compared with PPT (ERα agonist) and DPN (ERβ agonist), G1 (GPER agonist) significantly inhibited TSLP, up‐regulated occludin, and restored E‐cadherin. siGPER and TEER assays suggested that GPER was pivotal for the flavonoids on the epithelial barrier integrity. Finally, G1 attenuated allergic lung inflammation, which could be abolished by G15. Our data demonstrated that 2 flavonoids in Radix Astragali could alleviate allergic asthma by protecting epithelial integrity via regulating GPER, and activating GPER might be a possible therapeutic strategy against allergic inflammation.