AUTHOR=Song Yi , Wu Qian , Jiang Huojun , Hu Aihao , Xu Lingqi , Tan Caiping , Zhang Biao , Yu Rongming , Qiu Yizhen , Wang Xin , Yang Wenzhong 

TITLE=The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.764247

DOI=10.3389/fphar.2021.764247

ISSN=1663-9812

ABSTRACT=Purpose：The purpose of the present study was to estimate the effect of Shionone(SHI) on sepsis-induced acute lung injury(ALI). 
Methods：The cecal ligation and puncture (CLP) surgery was performed to induce sepsis in mice. 
The pulmonary H & E staining, Wet/Dry ratio, MPO activity and survival rate were detected. The RAW 264.7 cells were treated with SHI and stimulated with LPS. The cells were also overexpressed by ECM1 adenovirus. The relative levels of GM-CSF, IL-6, IL-1β, TNF-α, IL-10, TGF-β in serum and supernatant were measured by ELISA. The protein expressions of ECM1, p-STAT5, STAT5, p-NF-κB, NF-κB, Arg1, CD206, CD16/32 and iNOS in CLP-induced lung tissues and LPS-induced cells were detected by western blot. The cell counts of Ly6G, F4/80, CD16/32 and CD206 were evaluated by flow cytometry. The ECM1 expression was also observed by immunohistochemistry and immunofluorescence staining.
Results：As a result, the histopathological change, pulmonary edema and MPO activity were relieved by SHI. SHI treatment increased the percent of neutrophil and macrophage in BALF. Besides, the SHI administration inhibited pro-inflammatory cytokines and M1 phenotype indices, as well as augmented the anti-inflammatory cytokines and M2 phenotype indices. SHI also attenuated ECM1/STAT5/NF-κB pathway both in vivo and in vitro. The overexpression of ECM1 confirmed that the regulated effect of SHI was due to ECM1 signaling. 
Conclusion：In conclusion, the presented study suggested that SHI ameliorated sepsis-induced ALI by screwing M1 phenotype to M2 phenotype macrophage via ECM1/STAT5/NF-κB pathway.