Chrysophanol alleviates acute lung injury caused by Klebsiella pneumoniae infection by inhibiting pro-inflammatory cytokine production
Fei Jiang
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, P. R. China
Search for more papers by this authorJiebang Jiang
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorWenping He
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorGuokai Dong
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou Medical University, Xuzhou, P. R. China
Search for more papers by this authorNana Xu
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Laboratory of Morphology, Xuzhou Medical University, Xuzhou, P. R. China
Search for more papers by this authorLi Meng
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorYunyun Zhao
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorMeng Wang
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorCorresponding Author
Shirui Tan
Center of Life Sciences, School of Life Sciences, Yunnan University, Kunming, P. R. China
Correspondence
Rongpeng Li and Yongping Shi, Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Xuzhou 221116, P. R. China.
Email: [email protected], [email protected]
Shirui Tan, Center of Life Sciences, School of Life Sciences, Yunnan University, Yunnan, Kunming 650500, P. R. China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yongping Shi
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Correspondence
Rongpeng Li and Yongping Shi, Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Xuzhou 221116, P. R. China.
Email: [email protected], [email protected]
Shirui Tan, Center of Life Sciences, School of Life Sciences, Yunnan University, Yunnan, Kunming 650500, P. R. China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Rongpeng Li
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Jiangsu Xenon Life Science Research Institute, Xuzhou, P. R. China
Correspondence
Rongpeng Li and Yongping Shi, Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Xuzhou 221116, P. R. China.
Email: [email protected], [email protected]
Shirui Tan, Center of Life Sciences, School of Life Sciences, Yunnan University, Yunnan, Kunming 650500, P. R. China.
Email: [email protected]
Search for more papers by this authorFei Jiang
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, P. R. China
Search for more papers by this authorJiebang Jiang
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorWenping He
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorGuokai Dong
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou Medical University, Xuzhou, P. R. China
Search for more papers by this authorNana Xu
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Laboratory of Morphology, Xuzhou Medical University, Xuzhou, P. R. China
Search for more papers by this authorLi Meng
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorYunyun Zhao
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorMeng Wang
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Search for more papers by this authorCorresponding Author
Shirui Tan
Center of Life Sciences, School of Life Sciences, Yunnan University, Kunming, P. R. China
Correspondence
Rongpeng Li and Yongping Shi, Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Xuzhou 221116, P. R. China.
Email: [email protected], [email protected]
Shirui Tan, Center of Life Sciences, School of Life Sciences, Yunnan University, Yunnan, Kunming 650500, P. R. China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yongping Shi
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Correspondence
Rongpeng Li and Yongping Shi, Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Xuzhou 221116, P. R. China.
Email: [email protected], [email protected]
Shirui Tan, Center of Life Sciences, School of Life Sciences, Yunnan University, Yunnan, Kunming 650500, P. R. China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Rongpeng Li
Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, P. R. China
Jiangsu Xenon Life Science Research Institute, Xuzhou, P. R. China
Correspondence
Rongpeng Li and Yongping Shi, Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Xuzhou 221116, P. R. China.
Email: [email protected], [email protected]
Shirui Tan, Center of Life Sciences, School of Life Sciences, Yunnan University, Yunnan, Kunming 650500, P. R. China.
Email: [email protected]
Search for more papers by this authorFei Jiang, Jiebang Jiang and Wenping He contributed equally to this work.
Abstract
Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.
CONFLICT OF INTEREST STATEMENT
The authors declared that there was no conflict of interest regarding the publication of this paper.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
| Filename | Description |
|---|---|
| ptr7792-sup-0001-Figures.docxWord 2007 document , 134.3 KB | Figure S1. Chemical characterization of Chrysophanol. Figure S2. Viability and half maximal inhibitory concentration (IC50) of MH-S cells were determined by MTT assay. The IC50 was 119.5 μM (A). There was no obvious cytolethal induced by Chr on cells in the 3.125 μM-50 μM Chr-treatment group (B) and 10 μM dexamethasone treatment group. (***p < 0.001). Figure S3. The effect of the vehicle on cell viability. There was no statistically significant difference in cell viability in the vehicle group (92.22 ± 1.688) compared with the control group (100 ± 4.562) (p = 0.1409). Figure S4. The effect of the Chr and dexamethasone (positive control) on cell viability. Dexamethasone has a good protective effect on Klebsiella pneumoniae (KP) infection. The results showed no statistically significant difference in cell viability compared with the control group (p = 0.9954) and a significant difference in cell viability compared with the KP group (*p < 0.05, ***p < 0.001). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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