Synergistic Effects of Azithromycin and STING Agonist Promote IFN-I Production by Enhancing the Activation of STING-TBK1 Signaling.
TANK binding kinase 1
azithromycin
stimulator of interferon genes
type-I interferon
Journal
Journal of experimental pharmacology
ISSN: 1179-1454
Titre abrégé: J Exp Pharmacol
Pays: New Zealand
ID NLM: 101530345
Informations de publication
Date de publication:
2023
2023
Historique:
received:
25
08
2023
accepted:
28
10
2023
medline:
7
11
2023
pubmed:
7
11
2023
entrez:
7
11
2023
Statut:
epublish
Résumé
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. Therefore, this study aims to evaluate the role of AZM and STING on IFN-I responses in macrophages. 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. 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. 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.
Sections du résumé
Background
UNASSIGNED
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.
Objective
UNASSIGNED
Therefore, this study aims to evaluate the role of AZM and STING on IFN-I responses in macrophages.
Methods
UNASSIGNED
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.
Results
UNASSIGNED
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.
Conclusion
UNASSIGNED
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.
Identifiants
pubmed: 37933302
doi: 10.2147/JEP.S433181
pii: 433181
pmc: PMC10625772
doi:
Types de publication
Journal Article
Langues
eng
Pagination
407-421Informations de copyright
© 2023 Petcharat et al.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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