Corticotropin-releasing factor induces inflammatory cytokines via the NLRP6-inflammatory cytokine axis in a murine model of irritable bowel syndrome
Lei Min Yu
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
Lei Min Yu and Ke Jia Zhao contributed equally to this work.Search for more papers by this authorKe Jia Zhao
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Lei Min Yu and Ke Jia Zhao contributed equally to this work.Search for more papers by this authorShuang Shuang Wang
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Search for more papers by this authorXi Wang
The Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Search for more papers by this authorCorresponding Author
Bin Lu
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Correspondence
Bin LU, Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Hangzhou, Zhejiang Province 310006, China.
Email: [email protected]
Search for more papers by this authorLei Min Yu
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
Lei Min Yu and Ke Jia Zhao contributed equally to this work.Search for more papers by this authorKe Jia Zhao
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Lei Min Yu and Ke Jia Zhao contributed equally to this work.Search for more papers by this authorShuang Shuang Wang
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Search for more papers by this authorXi Wang
The Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Search for more papers by this authorCorresponding Author
Bin Lu
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
Correspondence
Bin LU, Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Hangzhou, Zhejiang Province 310006, China.
Email: [email protected]
Search for more papers by this authorFunding information Medical and Health Science and Technology Project of Zhejiang Province, Grant/Award Numbers: Nos. 2019310040, 2019311827; National Natural Science Foundation of China, Grant/Award Numbers: Nos. 81470814, 81400594
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.
CONFLICTS OF INTEREST
None.
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