Qing Huang, Jia-Wen Liu, Hai-Bin Dong, Zheng-Jie Wei, Jin-Zhe Liu, Yu-Tang Ren, Xuan Jiang, Bo Jiang
{"title":"肠系膜脂肪组织B淋巴细胞通过介导肠热亡促进重症急性胰腺炎肠损伤。","authors":"Qing Huang, Jia-Wen Liu, Hai-Bin Dong, Zheng-Jie Wei, Jin-Zhe Liu, Yu-Tang Ren, Xuan Jiang, Bo Jiang","doi":"10.1016/j.hbpd.2023.11.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Visceral adipose tissue<span><span> (VAT) has been linked to the severe acute pancreatitis (SAP) prognosis, although the underlying mechanism remains unclear. It has been reported that pyroptosis worsens SAP. The present study aimed to verify whether mesenteric adipose tissue (MAT, a component of VAT) can cause secondary </span>intestinal injury through the pyroptotic pathway.</span></p></div><div><h3>Methods</h3><p>Thirty-six male Sprague Dawley (SD) rats were divided into six different groups. Twelve rats were randomly divided into the SAP and control groups. We monitored the changes of MAT and B lymphocytes infiltration<span> in MAT of SAP rats. Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution (PBS). The remaining twelve SAP rats were first injected with MAT B lymphocytes, and then with MCC950 (NLRP3 inhibitor) or PBS. We collected blood and tissue samples from pancreas, gut and MAT for analysis.</span></p></div><div><h3>Results</h3><p><span><span>Compared to the control rats, the SAP group showed inflammation in MAT, including higher expression of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), lower expression of IL-10, and histological changes. Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not </span>T lymphocytes and macrophages. The SAP rats also exhibited intestinal injury, characterized by lower expression of zonula occludens-1 (ZO-1) and </span>occludin<span><span>, higher levels of lipopolysaccharide<span> and diamine oxidase, and pathological changes. The expression of </span></span>NLRP3<span> and n-GSDMD, which are responsible for pyroptosis, was increased in the intestine of SAP rats. The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT. The upregulation of pyroptosis reduced tight junction in the intestine, which contributed to the SAP progression, including higher inflammatory indicators and worse histological changes. The administration of MCC950 to SAP + MAT B rats downregulated pyroptosis, which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.</span></span></p></div><div><h3>Conclusions</h3><p>In SAP, MAT B lymphocytes aggravated local inflammation, and promoted the injury to the intestine through the enteric pyroptotic pathway.</p></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"23 3","pages":"Pages 300-309"},"PeriodicalIF":3.6000,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis\",\"authors\":\"Qing Huang, Jia-Wen Liu, Hai-Bin Dong, Zheng-Jie Wei, Jin-Zhe Liu, Yu-Tang Ren, Xuan Jiang, Bo Jiang\",\"doi\":\"10.1016/j.hbpd.2023.11.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Visceral adipose tissue<span><span> (VAT) has been linked to the severe acute pancreatitis (SAP) prognosis, although the underlying mechanism remains unclear. It has been reported that pyroptosis worsens SAP. The present study aimed to verify whether mesenteric adipose tissue (MAT, a component of VAT) can cause secondary </span>intestinal injury through the pyroptotic pathway.</span></p></div><div><h3>Methods</h3><p>Thirty-six male Sprague Dawley (SD) rats were divided into six different groups. Twelve rats were randomly divided into the SAP and control groups. We monitored the changes of MAT and B lymphocytes infiltration<span> in MAT of SAP rats. Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution (PBS). The remaining twelve SAP rats were first injected with MAT B lymphocytes, and then with MCC950 (NLRP3 inhibitor) or PBS. We collected blood and tissue samples from pancreas, gut and MAT for analysis.</span></p></div><div><h3>Results</h3><p><span><span>Compared to the control rats, the SAP group showed inflammation in MAT, including higher expression of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), lower expression of IL-10, and histological changes. Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not </span>T lymphocytes and macrophages. The SAP rats also exhibited intestinal injury, characterized by lower expression of zonula occludens-1 (ZO-1) and </span>occludin<span><span>, higher levels of lipopolysaccharide<span> and diamine oxidase, and pathological changes. The expression of </span></span>NLRP3<span> and n-GSDMD, which are responsible for pyroptosis, was increased in the intestine of SAP rats. The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT. The upregulation of pyroptosis reduced tight junction in the intestine, which contributed to the SAP progression, including higher inflammatory indicators and worse histological changes. The administration of MCC950 to SAP + MAT B rats downregulated pyroptosis, which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.</span></span></p></div><div><h3>Conclusions</h3><p>In SAP, MAT B lymphocytes aggravated local inflammation, and promoted the injury to the intestine through the enteric pyroptotic pathway.</p></div>\",\"PeriodicalId\":55059,\"journal\":{\"name\":\"Hepatobiliary & Pancreatic Diseases International\",\"volume\":\"23 3\",\"pages\":\"Pages 300-309\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2023-11-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatobiliary & Pancreatic Diseases International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1499387223002199\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatobiliary & Pancreatic Diseases International","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1499387223002199","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis
Background
Visceral adipose tissue (VAT) has been linked to the severe acute pancreatitis (SAP) prognosis, although the underlying mechanism remains unclear. It has been reported that pyroptosis worsens SAP. The present study aimed to verify whether mesenteric adipose tissue (MAT, a component of VAT) can cause secondary intestinal injury through the pyroptotic pathway.
Methods
Thirty-six male Sprague Dawley (SD) rats were divided into six different groups. Twelve rats were randomly divided into the SAP and control groups. We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats. Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution (PBS). The remaining twelve SAP rats were first injected with MAT B lymphocytes, and then with MCC950 (NLRP3 inhibitor) or PBS. We collected blood and tissue samples from pancreas, gut and MAT for analysis.
Results
Compared to the control rats, the SAP group showed inflammation in MAT, including higher expression of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), lower expression of IL-10, and histological changes. Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages. The SAP rats also exhibited intestinal injury, characterized by lower expression of zonula occludens-1 (ZO-1) and occludin, higher levels of lipopolysaccharide and diamine oxidase, and pathological changes. The expression of NLRP3 and n-GSDMD, which are responsible for pyroptosis, was increased in the intestine of SAP rats. The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT. The upregulation of pyroptosis reduced tight junction in the intestine, which contributed to the SAP progression, including higher inflammatory indicators and worse histological changes. The administration of MCC950 to SAP + MAT B rats downregulated pyroptosis, which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.
Conclusions
In SAP, MAT B lymphocytes aggravated local inflammation, and promoted the injury to the intestine through the enteric pyroptotic pathway.
期刊介绍：
Hepatobiliary & Pancreatic Diseases International (HBPD INT) (ISSN 1499-3872 / CN 33-1391/R) a bimonthly journal published by First Affiliated Hospital, Zhejiang University School of Medicine, China. It publishes peer-reviewed original papers, reviews and editorials concerned with clinical practice and research in the fields of hepatobiliary and pancreatic diseases. Papers cover the medical, surgical, radiological, pathological, biochemical, physiological and historical aspects of the subject areas under the headings Liver, Biliary, Pancreas, Transplantation, Research, Special Reports, Editorials, Review Articles, Brief Communications, Clinical Summary, Clinical Images and Case Reports. It also deals with the basic sciences and experimental work. The journal is abstracted and indexed in SCI-E, IM/MEDLINE, EMBASE/EM, CA, Scopus, ScienceDirect, etc.
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