Dual-directional Regulation Effects of Mannose on Inflammatory Response of Macrophages

WU Hui-juan; WEI Qu-xing; ZHANG Sheng-xi; HU Yin-ming; WANG Le-xun

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Dual-directional Regulation Effects of Mannose on Inflammatory Response of Macrophages

更新时间：2023-11-01

- Dual-directional Regulation Effects of Mannose on Inflammatory Response of Macrophages
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 41, Issue 4, Pages: 549-557(2020)
- 作者机构：
  
  广东省代谢病中西医结合研究中心//广东省代谢性疾病中医药防治重点实验室//粤港澳联合代谢病重点实验室//广东药科大学中医药研究院，广东广州 510006
- 作者简介：
  
  WANG Le-xun; E-mail: wanglexun123456@163.com
- 基金信息：
- DOI：
  CLC： R392.12
- Received：16 January 2020，
  
  Published：15 July 2020
- 稿件说明：
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吴惠娟,韦曲星,张盛昔等.甘露糖对巨噬细胞炎症反应的双向调节作用[J].中山大学学报（医学科学版）,2020,41(04):549-557.

WU Hui-juan,WEI Qu-xing,ZHANG Sheng-xi,et al.Dual-directional Regulation Effects of Mannose on Inflammatory Response of Macrophages[J].Journal of Sun Yat-sen University(Medical Sciences),2020,41(04):549-557.
吴惠娟,韦曲星,张盛昔等.甘露糖对巨噬细胞炎症反应的双向调节作用[J].中山大学学报（医学科学版）,2020,41(04):549-557. DOI：

WU Hui-juan,WEI Qu-xing,ZHANG Sheng-xi,et al.Dual-directional Regulation Effects of Mannose on Inflammatory Response of Macrophages[J].Journal of Sun Yat-sen University(Medical Sciences),2020,41(04):549-557. DOI：

摘要

目的

探讨甘露糖（Man）对炎症反应的调控及其机制，为甘露糖在炎症疾病中的应用提供依据。

方法

利用不同浓度的甘露糖处理RAW264.7巨噬细胞24 h或48 h，细胞计数检测增殖情况。低浓度（2 mmol/L）和高浓度（20 mmol/L）Man预处理RAW264.7细胞12 h，然后脂多糖（LPS）处理8 h或24 h，收集mRNA、蛋白质及培养上清，通过Q-PCR、Western blot和ELISA检测炎症相关指标以及甘露糖受体（CD206）的变化。

结果

在5 mmol/L以下，细胞增殖随Man的浓度增加而增加；在5 mmol/L以上，则相反。和LPS处理相比，LPS + 甘露糖2 mmol/L（Man2）能够增高IL-1β、IL-12和TNF-α的mRNA水平以及蛋白水平（均

0.05）；LPS + Man20显著抑制IL-1β、IL-12、TNF-α、IL-6和CCL2的mRNA水平和蛋白水平（均

0.05）。网络药理学预测甘露糖及其代谢产物的潜在作用靶点有包括AKT和STAT3在内的20个蛋白。Man2可协同LPS刺激AKT和STAT3的磷酸化（均

0.05），而Man20可抑制LPS诱导的AKT、p65和ERK磷酸化水平的增加（均

0.05）。单独甘露糖处理可抑制AKT、STAT3和p65的磷酸化（均

0.05）。

结论

不同浓度的甘露糖对炎症反应具有不同的作用。低浓度甘露糖能够促进LPS诱导的巨噬细胞炎症反应，而高浓度的甘露糖具有抑制LPS诱导的炎症反应，其机制与调控AKT、STAT3、p65和ERK的活性有关。

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

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

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

0.05) were increased in Man2 + LPS group and the phosphorylation levels of AKT

p65 and ERK (all

0.05) were decreased in Man20 + LPS group compared with LPS group. The phosphorylation levels of AKT

p65 and STAT3 (all

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.

关键词

Keywords

references

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