STING positively regulates human ORMDL3 expression through TBK1-IRF3-STAT6 complex mediation
- Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu Province (China)
- The First Clinical Medical School, Nanjing Medical University, Nanjing 210029, Jiangsu Province (China)
Highlights: • STING and ORMDL3 genes expression was increased in patients with recurrent wheeze. • STING upregulates ORMDL3 expression and promoter activity in cells. • ORMDL3 is positively associated with the STING-TBK1-IRF3/STAT6 signaling pathway. • STING increases the ORMDL3 expression in asthma and recurrent wheeze by promoting both the expression and activity of the TBK1-IRF3-STAT6 complex. 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.
- OSTI ID:
- 23082609
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 370; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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