Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism.
10.19746/j.cnki.issn.1009-2137.2023.03.039
- Author:
Xi-Xi LIU
1
;
Chen-Cheng LI
1
;
Jing YANG
1
;
Wei-Guang ZHANG
1
;
Re-Ai-La JIANATI
1
;
Xiao-Li ZHANG
1
;
Zu-Qiong XU
2
;
Xing-Bin DAI
2
;
Fang TIAN
3
;
Bi-Qing CHEN
4
;
Xue-Jun ZHU
5
Author Information
1. The Affiliated Hospital of Nanjing University of Chinese Medicine, The First Clinical Medical College of Nanjing University of Chinese Medicine Nanjing 210029, Jiangsu Province, China.
2. Department of Hematology, The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, Jiangsu Province, China.
3. Central Laboratory, The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, Jiangsu Province, China.
4. Central Laboratory, The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, Jiangsu Province, China,E-mail: chenbiqing333@163.com.
5. Department of Hematology, The Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, Jiangsu Province, China,E-mail：zhuxuejun@njucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Toll-like receptor 4;
cinobufotalin;
inflammatory factor;
monocyte/macrophage
- MeSH:
Humans;
Toll-Like Receptor 4/metabolism*;
Myeloid Differentiation Factor 88/genetics*;
Macrophages/metabolism*;
Cytokines/metabolism*;
Lipopolysaccharides/pharmacology*;
NF-kappa B
- From:
Journal of Experimental Hematology
2023;31(3):880-888
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.
METHODS:THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.
RESULTS:1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.
CONCLUSION:Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.
