Melatonin inhibits bile acids-initiated Cxcl2 expression through JNK/c-Jun signalling pathway

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Melatonin inhibits bile acids-initiated Cxcl2 expression through JNK/c-Jun signalling pathway

Basic Medicine | 更新时间：2026-01-09

- Melatonin inhibits bile acids-initiated Cxcl2 expression through JNK/c-Jun signalling pathway
- Journal of Army Medical University Vol. 44, Issue 8, Pages: 782-788(2022)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院消化内科，代谢性肝病中心和胆汁淤积肝病中心
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Distinguished Young Scholars of China(81922012);the Outstanding Youth Foundation of Chongqing(cstc2021jcyj-jqX0005)
- DOI：10.16016/j.2097-0927.202201199
  CLC： R575;R966;R977.1
- Received：21 January 2022，
  
  Revised：2022-03-11，
  
  Published：30 April 2022
- 稿件说明：
移动端阅览
Ya TAN, Wan TANG, Ziqian XU, et al. Melatonin inhibits bile acids-initiated Cxcl2 expression through JNK/c-Jun signalling pathway[J]. Journal of Army Medical University, 2022, 44(8): 782-788.
DOI：

Ya TAN, Wan TANG, Ziqian XU, et al. Melatonin inhibits bile acids-initiated Cxcl2 expression through JNK/c-Jun signalling pathway[J]. Journal of Army Medical University, 2022, 44(8): 782-788. DOI： 10.16016/j.2097-0927.202201199.

摘要

目的

2

研究褪黑素抑制胆汁酸诱导趋化因子Cxcl2表达的分子调控机制。

方法

2

喂养小鼠含有1%胆酸(cholic acid，CA)的饲料2周，构建胆汁淤积小鼠模型，给予褪黑素腹腔注射(100 mg/kg，1次/d)。收集肝组织后HE染色，根据Scheuer系统进行病理组织学评分。采用Real-time qPCR及Western blot方法检测褪黑素对小鼠肝脏内Cxcl2、Cxcr2、Mpo、c-Jun表达的影响。使用免疫组化方法检测小鼠肝脏内c-Jun的表达。分离并培养小鼠原代肝细胞，使用结合型胆汁酸TCA联合褪黑素处理小鼠原代肝细胞，在体外水平进一步探索褪黑素抑制胆汁酸诱导的Cxcl2表达的机制。使用JNK激动剂Anisomycin和褪黑素共同处理小鼠原代肝细胞，检测趋化因子Cxcl2表达。

结果

2

褪黑素给药明显减轻胆汁淤积诱导的炎症性肝损伤(

P

<

0.05)。褪黑素明显抑制胆汁淤积小鼠肝脏内趋化因子Cxcl2及其受体Cxcr2表达，并抑制肝脏内中性粒细胞标志物Mpo和转录因子c-Jun的表达(

P

<

0.05)。褪黑素显著减少TCA诱导的小鼠原代肝细胞内趋化因子Cxcl2的表达(

P

<

0.05)。J

NK激动剂Anisomycin逆转褪黑素对Cxcl2的抑制作用(

P

<

0.05)。

结论

2

褪黑素通过抑制JNK/c-Jun信号通路来降低胆汁酸诱导的趋化因子Cxcl2表达。

Abstract

Objective

2

To investigate the underlying molecular mechanism by which melatonin suppresses bile acids (BAs)-initiated expression of chemokine C-X-C motif chemokine ligand 2 (Cxcl2).

Methods

2

Mice were fed a 1% cholic acid (CA)-supplemented diet for 2 weeks to establish a model of cholestatic disease

and were given an intraperitoneal injection of melatonin (100 mg/kg) once a day for 2 weeks. Then

the liver tissues were collected for HE staining

and the liver histology was scored using the Scheuer scoring system. Effects of melatonin on the expression of Cxcl2

Cxcr2

myeloperoxidase (Mpo) and c-Jun in the liver tissues at mRNA and protein levels were detected by real-time qPCR and Western blotting. The expression of c-Jun in the liver tissues was measured by immunohistochemical assay. Primary mouse hepatocytes were isolated and cultured

and then treated with taurine-conjugated bile acid

taurocholic acid (TCA) and melatonin in order to explore the mechanism of melatonin reducing BAs-initiated Cxcl2 expression. Furthermore

these primarily cultured cells were treated with anisomycin (JNK agonist) and melatonin to further detect the expression of Cxcl2.

Results

2

Melatonin treatment significantly ameliorated cholestasis-induced inflammatory liver injury (

P

<

0.05)

and reduced the elevated expression of Cxcl2

Cxcr2

Mpo(a biomarker of neutrophils) and the transcription factor c-Jun in the livers of cholestatic disease mice (

P

<

0.05). In addition

melatonin suppressed TCA-stimulated Cxcl2 in primary mouse hepatocytes (

P

<

0.05). Anisomycin reversed melatonin-inhibited Cxcl2 (

P

<

0.05).

Conclusion

2

Mela

tonin treatment can decrease BAs-initiated expression of Cxcl2

via

inhibition of JNK/c-Jun signaling pathway in mouse hepatocytes.

关键词

Keywords

references

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