Maxing Shigan Decoction Regulates Immune Inflammatory Response of Adenovirus Pneumonia by Inhibiting cGAS-STING Pathway.

OBJECTIVE

To investigate whether Maxing Shigan Decoction (MSD) regulates the immune-inflammatory response of adenovirus pneumonia (AVP) by inhibiting the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway.

METHODS

A mouse model of AVP was induced by intranasal instillation of human adenovirus type 3 (Ad3), and Raw264.7 cells were infected with Ad3 to establish an in vitro model. The in vivo and in vitro experiments both included 6 groups: control, model, ribavirin (RIB), and low- (MSD-L), medium- (MSD-M), and high-dose MSD (MSD-H) groups. Moreover, the cGAS-STING pathway agonist SR-717 was used during the cell experiment. Hematoxylin and eosin (HE) staining was conducted to identify pathological changes in the lung tissue of AVP mice. The quantity of CD3+CD8+ T cells in the mouse lung tissue was evaluated using flow cytometry. The expression levels of cGAS, STING, interferon-β (IFN-β), TANK binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3) were assessed by Western blot for protein levels and quantitative polymerase chain reaction for mRNA levels.

RESULTS

In vivo, MSD and RIB significantly reduced lung tissue inflammation in the AVP mouse model, and reduced the excessive immune response mediated by CD3+CD8+ T cells (P<0.01). The cGAS, STING, IFN-β, TBK1, and IRF3 protein and mRNA levels were markedly elevated in model mice (P<0.01), while treatment with MSD and RIB significantly reduced these levels (P<0.01). In vitro experiments showed the similar results of levels of cGAS, STING, IRF3, TBK1, and IFN-β proteins and mRNAs. However, these levels significantly decreased with MSD and RIB treatment were restored after treatment with SR-717 (P<0.01).

CONCLUSIONS

MSD modulated the immune inflammatory response in AVP by inhibiting the cGAS-STING pathway. It protected lung tissue from damage caused by excessive immune responses and inflammatory reactions.