Abstract
Background: Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)'s role has been shown to drive immune regulation and inflammation in many human diseases. However, the exact mechanism of action of IFIT1 in AS is unclear, and the specific mechanism of action on METs is also unknown. In this study, we will explore the potential mechanisms of IFIT1 in the formation of METs during AS.
Methods: We downloaded GSE100927, GSE193336, GSE159677, IRGs, and METs-related genes for analysis and used qRT-PCR, flow cytometry, and immunofluorescence to detect the expression levels of IFIT1 and METs in plaques from AS patients and mice. The potential association of IFIT1 and METs in macrophages was similarly verified in LPS-induced macrophages. After IFIT1 silencing, the expression levels of METs were detected using qRT-PCR, flow cytometry, immunofluorescence, and WB. In addition, we delved into the potential mechanisms to detect the expression of the STING-TBK1 pathway and explored the interaction between IFIT1 and the STING-TBK1 pathway.
Results: Our results showed that IFIT1 was upregulated in AS patients, mouse plaque tissues, and LPS-induced macrophages. The same changes were observed in METs.The decrease in METs after IFIT1 silencing suggests that IFIT1 is involved in the regulation of macrophages through METs. Notably, with the decrease in IFIT1 levels, we observed a corresponding decrease in the STING-TBK1 pathway, which decreased accordingly, suggesting some connection between IFIT1, STING-TBK1, and METs. Validation of the effect of STING-TBK1 on a macrophage basis showed that the STING activator SR-717 increased the expression of METs, while the STING inhibitor H-151 had the opposite result. Interestingly, we added SR-717 and H-151 to si-IFIT1, respectively, and the same changes occurred in METs.
Conclusion: In summary, our study suggests that IFIT1 activates METs through the STING-TBK1 pathway, thereby aggravating AS.