1. Paeonol attenuates inflammation by targeting HMGB1 through upregulating miR-339-5p
- Author
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Junli Lin, Liyan Mei, Qin Xu, Peng Ye, Huina Huang, Xia Liu, Jifei Miao, Meihong He, Chaoying Zhang, Quan Wen, Xiaojing Zhou, Hui Li, Dongfeng Chen, Kai Zhao, Chun Li, Sen Ye, and Jianhong Zhou
- Subjects
Lipopolysaccharides ,Anti-Inflammatory Agents ,lcsh:Medicine ,Inflammation ,IκB kinase ,Pharmacology ,HMGB1 ,Paeonia ,Article ,Proinflammatory cytokine ,Sepsis ,chemistry.chemical_compound ,Mice ,Western blot ,In vivo ,medicine ,Animals ,Humans ,HMGB1 Protein ,lcsh:Science ,Multidisciplinary ,biology ,medicine.diagnostic_test ,Chemistry ,lcsh:R ,NF-kappa B ,Acetophenones ,medicine.disease ,Disease Models, Animal ,MicroRNAs ,RAW 264.7 Cells ,Gene Expression Regulation ,biology.protein ,lcsh:Q ,medicine.symptom ,Paeonol ,Drugs, Chinese Herbal - Abstract
Sepsis is a life-threatening disease caused by infection. Inflammation is a key pathogenic process in sepsis. Paeonol, an active ingredient in moutan cortex (a Chinese herb), has many pharmacological activities, such as anti-inflammatory and antitumour actions. Previous studies have indicated that paeonol inhibits the expression of HMGB1 and the transcriptional activity of NF-κB. However, its underlying mechanism is still unknown. In this study, microarray assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results confirmed that paeonol could significantly up-regulate the expression of miR-339-5p in RAW264.7 cells stimulated by LPS. Dual-luciferase assays indicated that miR-339-5p interacted with the 3′ untranslated region (3′-UTR) of HMGB1. Western blot, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analyses indicated that miR-339-5p mimic and siHMGB1 both negatively regulated the expression and secretion of inflammatory cytokines (e.g., HMGB1, IL-1β and TNF-α) in LPS-induced RAW264.7 cells. Studies have confirmed that IKK-β is targeted by miR-339-5p, and we further found that paeonol could inhibit IKK-β expression. Positive mutual feedback between HMGB1 and IKK-β was observed when we silenced HMGB1 or IKK-β. These results indicated that paeonol could attenuate the inflammation mediated by HMGB1 and IKK-β by upregulating miR-339-5p expression. In addition, we constructed CLP model mice by cecal ligation and puncture. Paeonol was used to intervene to investigate its anti-inflammatory effect in vivo. The results showed that paeonol could improve the survival rate of sepsis mice and protect the kidney of sepsis mice.
- Published
- 2019