Dual-directional Regulation Effects of Mannose on Inflammatory Response of Macrophages
- VernacularTitle:甘露糖对巨噬细胞炎症反应的双向调节作用
- Author:
Hui-juan WU
1
;
Qu-xing WEI
1
;
Sheng-xi ZHANG
1
;
Yin-ming HU
1
;
Le-xun WANG
1
Author Information
1. Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine// Guangdong Key Laboratory of Metabolic Disease Prevention and Treatment of Traditional Chinese Medicine// Joint Laboratory of Guangdong, Hong Kong and Macao on Glycolipid Metabolic Diseases// Institute of Chinese Medicine Sciences, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Publication Type:Journal Article
- Keywords:
mannose;
macrophage;
inflammation;
signal pathway
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(4):549-557
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the regulation and mechanism of mannose(Man) on inflammatory response, so as to provide the basis for application of Man in inflammatory diseases. 【Methods】 RAW264.7 macrophages were treated with different concentrations of Man for 24 h or 48 h, and the proliferation was detected by cell count. RAW264.7 cells were pretreated with low concentration(2 mmol/L) and high concentration(20 mmol/L) of Man for 12 h, followed by treatment with lipopolysaccharide(LPS) for 8 h or 24 h more. mRNA, protein and culture supernatant were collected, and the inflammation related cytokines, proteins and mannose receptor(CD206) were detected by Q-PCR, Western blot, and ELISA. 【Results】 The cell proliferation was increased with the increase of Man concentration under 5 mmol/L, while it was decreased with the increase of Man concentration over 5 mmol/L. Compared with LPS treatment, 2 mmol/L mannose(Man2) plus LPS increased the mRNA levels of IL-1β, IL-12 and TNF-α and the protein levels(all P<0.05), while Man20 + LPS treatment significantly decreased the mRNA levels of IL-1β, IL-12, TNF-α, IL-6, and CCL2 and the protein levels (all P<0.05). The potential targets of network pharmacology for Man and its metabolites were 20 proteins, including AKT and STAT3. Furthermore, the phosphorylation levels of AKT and STAT3(all P<0.05) were increased in Man2 + LPS group and the phosphorylation levels of AKT, p65 and ERK(all P<0.05) were decreased in Man20 + LPS group compared with LPS group. The phosphorylation levels of AKT, p65 and STAT3(all P<0.05) were decreased in Man20 group compared with control group. 【Conclusions】 Different concentrations of mannose have various effects on inflammatory response. Low concentration mannose promotes macrophage inflammatory response induced by LPS, while high concentration mannose inhibits LPS-induced inflammatory response. And this mechanism is related to the regulation of AKT, STAT3, p65, and ERK activities.
