Irisin inhibits neutrophil extracellular traps formation and protects against acute pancreatitis in mice
Fei Han,
Zi-fan Ding,
Xiao-lei Shi,
Qing-tian Zhu,
Qin-hao Shen,
Xing-meng Xu,
Jun-xian Zhang,
Wei-juan Gong,
Wei-ming Xiao,
Dan Wang,
Wei-wei Chen,
Liang-hao Hu,
Guo-tao Lu
Affiliations
Fei Han
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Zi-fan Ding
Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; International Sport Management, Health and Life Sciences, Northumbria University Newcastle, NE1 8ST, UK
Xiao-lei Shi
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Qing-tian Zhu
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Qin-hao Shen
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Xing-meng Xu
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Jun-xian Zhang
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Wei-juan Gong
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Wei-ming Xiao
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
Dan Wang
Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
Wei-wei Chen
Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; Corresponding author. Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Liang-hao Hu
Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China; Corresponding author. Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
Guo-tao Lu
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Corresponding author. Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Introduction: Irisin is a newly discovered myokine which links exercise to inflammation and inflammation-related diseases through macrophage regulation. However, the effect of irisin on the activity of inflammation related immune cells (such as neutrophils) has not been clearly described. Objectives: The objective of our study was to explore the effect of irisin on the neutrophil extracellular traps (NETs) formation. Methods: Phorbol-12-myristate-13-acetate (PMA) was used to construct a classic neutrophil inflammation model that was used to observe the formation of NETs in vitro. We studied the effect of irisin on NETs formation and its regulation mechanism. Subsequently, acute pancreatitis (AP) was used to verify the protective effect of irisin in vivo, which was an acute aseptic inflammatory response disease model closely related to NETs. Results: Our study found that addition of irisin significantly reduced the formation of NETs via regulation of the P38/MAPK pathway through integrin αVβ5, which might be the one of key pathways in NETs formation, and which could theoretically offset the immunoregulatory effect of irisin. Systemic treatment with irisin reduced the severity of tissue damage common in the disease and inhibited the formation of NETs in pancreatic necrotic tissue of two classical AP mouse models. Conclusion: The findings confirmed for the first time that irisin could inhibit NETs formation and protect mice from pancreatic injury, which further elucidated the protective effect of exercise on acute inflammatory injury.
