Unknown

Dataset Information

0

Calcitriol inhibits ROS-NLRP3-IL-1? signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells.


ABSTRACT: PURPOSE:The activation of ROS-NLRP3-IL-1? signaling axis induced by hyperosmotic stress (HS) has been recognized as a key priming stage of epithelial inflammation in dry eye pathogenesis. The current study aims to investigate whether calcitriol, the active metabolite of vitamin D3, could protect cells against HS-induced inflammation through modulating this critical step. METHODS:Human corneal epithelial cells (iHCECs) were cultured in hyperosmotic medium (450 mOsM) with various concentrations of calcitriol. Small interfering RNA (siRNA) was used to knock down the expression of vitamin D receptor (VDR) in iHCECs. NLRP3 activation and IL-1? generation were detected by RT-qPCR or ELISA, respectively. Oxidative stress markers including ROS and 8-OHdG were examined by fluorometric analysis. The nuclear translocation of NRF2 was assessed by western blotting. RESULTS:Calcitriol could protect cells against HS-induced injury through inhibiting ROS-NLRP3-IL-1? signaling axis. Calcitriol remarkably suppressed the expression of NLRP3 inflammasome related genes and the production of IL-1? in cells that were exposed to HS. It could also significantly attenuate HS-induced oxidative stress, shown as the reduced intracellular ROS generation and 8-OHdG staining cells after calcitriol treatment. Calcitriol induced the translocation of NRF2 to the nucleus, and thereby triggered the expression of several antioxidant enzymes. CONCLUSION:The current study indicated that calcitriol could inhibit the priming stage of HS-induced cellular inflammation, highlighting its potential capacity to prevent and mitigate dry eye related corneal inflammation at an earlier stage.

SUBMITTER: Dai Y 

PROVIDER: S-EPMC6313824 | BioStudies | 2019-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2016-01-01 | S-EPMC4725955 | BioStudies
2020-01-01 | S-EPMC7176120 | BioStudies
2020-01-01 | S-EPMC7471690 | BioStudies
1000-01-01 | S-EPMC6312447 | BioStudies
1000-01-01 | S-EPMC6249848 | BioStudies
2016-01-01 | S-EPMC4762577 | BioStudies
2018-01-01 | S-EPMC6111804 | BioStudies
2021-01-01 | S-EPMC7807058 | BioStudies
2019-01-01 | S-EPMC6874461 | BioStudies
2017-01-01 | S-EPMC5537437 | BioStudies