Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A2A Receptor Signaling |
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| Authors: | Jun Li Li Zhao Xie He Yi-Jun Zeng Shuang-Shuang Dai |
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| Affiliation: | 1. Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.; 2. Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing, China.; Vanderbilt University Medical Center, United States of America, |
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| Abstract: | Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccharide (LPS)-induced ALI in mice. After ALI, lung water content and histological signs of pulmonary injury were attenuated, whereas the PaO2/FIO2 (P/F) ratios were elevated significantly in the mice pretreated with SIN. Additionally, SIN markedly inhibited inflammatory cytokine TNF-α and IL-1β expression levels as well as neutrophil infiltration in the lung tissues of the mice. Microarray analysis and real-time PCR showed that SIN treatment upregulated adenosine A2A receptor (A2AR) expression, and the protective effect of SIN was abolished in A2AR knockout mice. Further investigation in isolated mouse neutrophils confirmed the upregulation of A2AR by SIN and showed that A2AR-cAMP-PKA signaling was involved in the anti-inflammatory effect of SIN. Taken together, these findings demonstrate an A2AR-associated anti-inflammatory effect and the protective role of SIN in ALI, which suggests a potential novel approach to treat ALI. |
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