Background
Azithromycin (AZM) is a macrolide antibiotic that exhibits anti-inflammatory and anti-viral infection properties by enhancing type-I interferon (IFN-I) responses. The stimulator of interferon genes (STING) can directly induce IFN-I production. However, elevated IFN-I induces auto-immune phenotypes such as systemic lupus erythematosus (SLE). The effects of AZM and STING on the production of IFN-I are unclear.
Conclusion
Our data suggest that AZM enhancement of IFN-I responses was STING dependent in DMXAA-stimulated macrophages. These data underline a novel approach to AZM action-mediated STING-TBK1 signaling for regulating IFN-I responses and may further augment the scientific basis and potential use of AZM in clinical applications.
Methods
RAW 264.7 macrophages were treated with AZM with and without a STING-agonist (DMXAA), and the maturation of macrophages was determined using flow cytometry. Gene expression and pro-inflammatory cytokines were analyzed using qPCR and ELISA, respectively. Moreover, protein expression was investigated using Western blot assays and immunofluorescence.
Objective
Therefore, this study aims to evaluate the role of AZM and STING on IFN-I responses in macrophages.
Results
Our results show that AZM significantly induced M1 phenotypes, promoting surface molecule expansion of CD80 and MHC-II and production of IL-6 and TNF-α cytokines on DMXAA-stimulated macrophages. Furthermore, we found that AZM-increased mRNA levels of interferon-stimulated genes (ISGs) could be due to the high expression of STNG-TBK1 signaling in the presence of DMXAA.