Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis
Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Hepatobiliary & pancreatic diseases international : HBPD INT - 23(2024), 3 vom: 11. Apr., Seite 300-309 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Qing [VerfasserIn] |
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| Links: |
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| Themen: |
Acute pancreatitis |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.hbpd.2023.11.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365480908 |
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| 100 | 1 | |a Huang, Qing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis |
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| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: In SAP, MAT B lymphocytes aggravated local inflammation, and promoted the injury to the intestine through the enteric pyroptotic pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute pancreatitis | |
| 650 | 4 | |a B lymphocyte | |
| 650 | 4 | |a Intestinal barrier | |
| 650 | 4 | |a Mesenteric adipose tissue | |
| 650 | 4 | |a Pyroptosis | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 700 | 1 | |a Liu, Jia-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Hai-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Zheng-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jin-Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Yu-Tang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Bo |e verfasserin |4 aut | |
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