House dust mite-induced endoplasmic reticulum stress mediates mucus
MUC5AC hyper secretion via TBK1-STAT6/NF-κB in asthmatic mice
Abstract
ABSTRACT Background Exposed to house dust mite (HDM) is known to be
associated with allergic asthma. Endoplasmic reticulum (ER) stress is
involved in the regulation of mucus hyper secretion. However, the
mechanism remains unclear. Our main goal was to investigate the
relationship of TBK1 pathway regulates the expression of MUC5AC under
the HDM induced ER stress promote allergic asthma. Methods Using HDM
induced allergic mice and stimulated over expression of MUC5AC in human
airway epithelial cells. We examined the mucus and the expression of ER
stress markers both in vivo and in vitro. Additionally, we investigated
whether TBK1, NF-κB, STAT6 play an important role in the HDM induced ER
stress promote airway mucus hyper secretion. Results Mice exposed to HDM
were identified ER stress, hyper secretion of mucus, and activated
TBK1-NF-κB/STAT6 signaling pathway in airway epithelial cells of
asthmatic mice. Similarly results had also been observed in the human
airway epithelial cells after exposed to HDM. Both in vivo and in vitro
study not only revealed that an anti-allergy drug, Amlexanox, reduced
super response of mucus and weaken TBK1-NF-κB/STAT6 signal of induced
asthma. But also indicated HDM induced ER stress result in over
production of MUC5AC, which can be decreased by the inhibition of TBK1,
NF-κB, STAT6, or even by using ER stress inhibitor 4-PBA, respectively.
Conclusions Our results show that TBK1-NF-κB/STAT6 plays a pivotal role
in the HDM induced ER stress result in over production of mucus protein
MUC5AC in the asthmatic airway.