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促肾上腺皮质素释放因子通过 NLRP6-炎性细胞因子轴在肠易激综合征的小鼠模型中诱导炎性细胞因子。

Corticotropin-releasing factor induces inflammatory cytokines via the NLRP6-inflammatory cytokine axis in a murine model of irritable bowel syndrome.

机构信息

Department of Gastroenterology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China.

Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.

出版信息

J Dig Dis. 2019 Mar;20(3):143-151. doi: 10.1111/1751-2980.12704. Epub 2019 Mar 5.

DOI:10.1111/1751-2980.12704
PMID:30663229
Abstract

OBJECTIVE

This study aimed to determine the effect of corticotropin-releasing factor (CRF) on regulating the NOD-like receptor pyrin domain-containing protein 6 (NLRP6)-inflammatory cytokine axis in a murine model of irritable bowel syndrome (IBS).

METHODS

C57BL/6 mice were subjected to water avoidance stress (WAS) for 1 h per day for 10 days, and the abdominal withdrawal reflex (AWR) and colonic inflammation were assessed. We also measured the levels of CRF, NLRP6 inflammasome components, myeloperoxidase, D-lactate, interleukin (IL)-1β, and IL-18. In vitro experiments with Caco-2 cell line were also performed. In addition, we assessed the effect of Clostridium butyricum (C. butyricum) on IBS mice.

RESULTS

IBS mice exhibited visceral hypersensitivity and inflammation, accompanied by increases in CRF, myeloperoxidase, D-lactate, IL-1β, and IL-18 levels, but a decrease in NLRP6 expression. In vitro data showed that CRF suppressed NLRP6, but induced IL-1β and IL-18 levels, in Caco-2 cells. C. butyricum restored CRF levels and maintained the NLRP6-inflammatory cytokine axis in IBS mice.

CONCLUSIONS

CRF induces the NLRP6-inflammatory cytokine axis in IBS mice. C. butyricum could be beneficial in controlling IBS.

摘要

目的

本研究旨在探讨促肾上腺皮质激素释放因子(CRF)对肠易激综合征(IBS)小鼠模型中 NOD 样受体含吡咯结构域蛋白 6(NLRP6)-炎症细胞因子轴的调节作用。

方法

将 C57BL/6 小鼠进行 10 天的每天 1 小时水回避应激(WAS),评估腹部回缩反射(AWR)和结肠炎症。我们还测量了 CRF、NLRP6 炎性体成分、髓过氧化物酶、D-乳酸、白细胞介素(IL)-1β和 IL-18 的水平。还进行了 Caco-2 细胞系的体外实验。此外,我们评估了丁酸梭菌(C. butyricum)对 IBS 小鼠的影响。

结果

IBS 小鼠表现出内脏高敏感性和炎症,伴随着 CRF、髓过氧化物酶、D-乳酸、IL-1β和 IL-18 水平的升高,但 NLRP6 表达降低。体外数据显示,CRF 抑制了 Caco-2 细胞中的 NLRP6,但诱导了 IL-1β和 IL-18 水平的升高。C. butyricum 恢复了 IBS 小鼠的 CRF 水平,并维持了 NLRP6-炎症细胞因子轴。

结论

CRF 诱导 IBS 小鼠的 NLRP6-炎症细胞因子轴。丁酸梭菌可能有益于控制 IBS。

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