Abstract
Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.
Highlights
Acute lung injury (ALI) and its more serious manifestation-acute respiratory distress syndrome (ARDS) are respiratory diseases characterized by acute hypoxemic respiratory distress and severe lung edema with normal cardiac filling pressures (Yang W. et al, 2020)
These results indicated that Tanreqing injection (TRQ) could prevent the progress of ALI
The results showed that TRQ protected against lung edema, lung injury, and inflammatory cell infiltration, alleviated inflammatory responses and oxidative stress, and inactivated STING-mediated IRF3/NF-κB signaling pathway in vivo and in vitro
Summary
Acute lung injury (ALI) and its more serious manifestation-acute respiratory distress syndrome (ARDS) are respiratory diseases characterized by acute hypoxemic respiratory distress and severe lung edema with normal cardiac filling pressures (Yang W. et al, 2020). Sepsis, aspiration, and trauma are the major causes of ALI/ARDS (Suresh et al, 2000). Despite improvements in therapy methods over the years, the mortality rate remains high. A prospective study conducted in 14 Brazilian ICU containing 7,133 patients showed that the mortality rate associated with ALI reached 49.2% (Caser et al, 2014). A study conducted in Japan indicated that the mortality of patients with ARDS was 38% (Fujishima et al, 2020). It is urgent to understand the pathophysiology of ALI/ARDS and find effective treatment
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