Open Access1,25( OH ) 2 D 3 blocks IFNβ production through regulating STING in epithelial layer of oral lichen planus
Author(s) -
Ge Xuejun,
Wang Yaxian,
Xie Hanting,
Li Ran,
Zhang Fang,
Zhao Bin,
Du Jie
Publication year - 2022
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.17409
Subject(s) - sting , stimulator of interferon genes , interferon , cytokine , transcription factor , oral lichen planus , calcitriol receptor , biology , vitamin d and neurology , immunology , chemistry , immune system , gene , endocrinology , innate immune system , biochemistry , engineering , aerospace engineering
Stimulator of interferon genes (STING) is reported to exert vital functions in inflammatory responses and autoimmune diseases. Nevertheless, the status and roles of STING in oral lichen planus (OLP) remain elusive. Here, we state that STING and its downstream cytokine interferon‐β (IFNβ) expression is boosted in the oral keratinocytes from patients suffering OLP in comparison with those from healthy participants. Mechanistically, transcription factor GATA‐binding protein 1 (GATA1) which is highly increased in diseased samples specifically interacts with its element in the promoter of STING to enhance STING transcripts. 1,25(OH) 2 D 3 , the active form of vitamin D, is capable of restricting STING and IFNβ increases in oral keratinocyte models resembling OLP in vitro. Moreover, there is a negative correlation between vitamin D receptor (VDR) and STING or IFNβ in human samples. Using plasmids and small interfering RNA transfection technologies, we find 1,25(OH) 2 D 3 regulates STING and IFNβ through a mechanism controlled by the hypoxia‐inducible factor‐1α (HIF‐1α)‐GATA1 axis. Collectively, our findings unveil that 1,25(OH) 2 D 3 lowers STING and IFNβ overexpression in the context of OLP.