Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8949730 | Experimental Cell Research | 2018 | 8 Pages |
Abstract
Orosomucoid 1-like protein 3 (ORMDL3) is an asthma candidate gene associated with virus-triggered recurrent wheeze. Stimulator of interferon gene (STING) controls TLR-independent cytosolic responses to viruses. However, the association of STING with ORMDL3 is unclear. Here, we have shown that ORMDL3 expression shows a linear correlation with STING in recurrent wheeze patients. In elucidating the molecular mechanisms of the ORMDL3-STING relationship, we found that STING promoted the transcriptional activity of ORMDL3, which was significantly associated with increased levels of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 6 (STAT6). Further study showed that via activation of TANK binding kinase 1 (TBK1), STING enhanced the phosphorylation and binding of IRF3 and STAT6, which upregulated ORMDL3 by binding to the promoter. Our results showed that STING positively regulated ORMDL3 through the TBK1-IRF3-STAT6 complex.
Keywords
IRF3TLRRSVqRT-PCRCTDCTTStat6TBK1dsDNAFBSDMEMORMDL3PBSNF-κBBSAdouble-stranded DNADulbecco's modified Eagle MediumHRVSmall interfering RNAsiRNAbovine serum albuminEBVIFNTANK binding kinase 1carboxy terminal domainC-terminal tailHuman rhinovirusfetal bovine serumendoplasmic reticulumInterferon regulatory factor 3interferon regulatory factorsnuclear factor κBSignal transducer and activator of transcription 6stimulator of interferon genesPhosphate-buffered salineGenome-wide association studiesGWASSTINGquantitative real-time PCRRespiratory syncytial virusRecurrent wheezeToll-like receptors
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Authors
Qian Cao, Chen-Xia Juan, Dao-Qi Zhang, Jia He, Yi-Zhi Cao, Asfia Banu Pasha, Jin-Ya Wang, Hai-Xiao Qi, Sheng Li, Rui Jin, Guo-Ping Zhou,