Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis

Abstract The release of inflammatory cytokines, that plays a dominant role in local pancreatic inflammation and systemic complications in severe acute pancreatitis (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP. This cu...

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Autores principales:	Xia Chen, Hong-Xian Zhao, Chao Bai, Xiang-Yu Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f9a2ac66e3e499f994cd96e7fc0145f
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spelling	oai:doaj.org-article:9f9a2ac66e3e499f994cd96e7fc0145f2021-12-02T11:52:33ZBlockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis10.1038/s41598-017-07094-y2045-2322https://doaj.org/article/9f9a2ac66e3e499f994cd96e7fc0145f2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07094-yhttps://doaj.org/toc/2045-2322Abstract The release of inflammatory cytokines, that plays a dominant role in local pancreatic inflammation and systemic complications in severe acute pancreatitis (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP. This current study aims to investigate possible role of HMGB1 in the intestinal mucosal barrier dysfunction of SAP, and the effect of anti-HMGB1 antibody treatment in intestinal mucosal injury in SAP. Our data revealed that the HMGB1 expression was significantly increased in AP mice induced by caerulein and LPS, and the inhibition of HMGB1 played a protective role in intestinal mucosal barrier dysfunction, reduced the serum level of other proinflammatory cytokines include IL-1β, IL-6, TNF-α. Next we investigated the downstream receptors involving in HMGB1 signaling. We found that the expressions of toll-like receptor (TLR) 4 and TLR9 were elevated in ileum of AP mice, the administration of HMGB1 neutralizing antibody significantly reduced the TLR4 and TLR9 expression. It was concluded that HMGB1 contributed the mechanism to the intestinal mucosal barrier dysfunction during AP. Blockade of HMGB1 by administration of HMGB1 neutralizing antibody may be a beneficial therapeutic strategy in improving intestinal mucosal barrier dysfunction in SAP.Xia ChenHong-Xian ZhaoChao BaiXiang-Yu ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xia Chen Hong-Xian Zhao Chao Bai Xiang-Yu Zhou Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
description	Abstract The release of inflammatory cytokines, that plays a dominant role in local pancreatic inflammation and systemic complications in severe acute pancreatitis (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP. This current study aims to investigate possible role of HMGB1 in the intestinal mucosal barrier dysfunction of SAP, and the effect of anti-HMGB1 antibody treatment in intestinal mucosal injury in SAP. Our data revealed that the HMGB1 expression was significantly increased in AP mice induced by caerulein and LPS, and the inhibition of HMGB1 played a protective role in intestinal mucosal barrier dysfunction, reduced the serum level of other proinflammatory cytokines include IL-1β, IL-6, TNF-α. Next we investigated the downstream receptors involving in HMGB1 signaling. We found that the expressions of toll-like receptor (TLR) 4 and TLR9 were elevated in ileum of AP mice, the administration of HMGB1 neutralizing antibody significantly reduced the TLR4 and TLR9 expression. It was concluded that HMGB1 contributed the mechanism to the intestinal mucosal barrier dysfunction during AP. Blockade of HMGB1 by administration of HMGB1 neutralizing antibody may be a beneficial therapeutic strategy in improving intestinal mucosal barrier dysfunction in SAP.
format	article
author	Xia Chen Hong-Xian Zhao Chao Bai Xiang-Yu Zhou
author_facet	Xia Chen Hong-Xian Zhao Chao Bai Xiang-Yu Zhou
author_sort	Xia Chen
title	Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
title_short	Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
title_full	Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
title_fullStr	Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
title_full_unstemmed	Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
title_sort	blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9f9a2ac66e3e499f994cd96e7fc0145f
work_keys_str_mv	AT xiachen blockadeofhighmobilitygroupbox1attenuatesintestinalmucosalbarrierdysfunctioninexperimentalacutepancreatitis AT hongxianzhao blockadeofhighmobilitygroupbox1attenuatesintestinalmucosalbarrierdysfunctioninexperimentalacutepancreatitis AT chaobai blockadeofhighmobilitygroupbox1attenuatesintestinalmucosalbarrierdysfunctioninexperimentalacutepancreatitis AT xiangyuzhou blockadeofhighmobilitygroupbox1attenuatesintestinalmucosalbarrierdysfunctioninexperimentalacutepancreatitis
_version_	1718395001226919936

Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis

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