Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.

Opiates are among the most prescribed drugs for pain management. However, morphine use or abuse results in significant gut bacterial translocation and predisposes patients to serious infections with gut origin. The mechanism underlying this defect is still unknown. In this report, we investigated th...

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Autores principales:	Jingjing Meng, Haidong Yu, Jing Ma, Jinghua Wang, Santanu Banerjee, Rick Charboneau, Roderick A Barke, Sabita Roy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56f75733eb584cd790e2410f436f5063
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spelling	oai:doaj.org-article:56f75733eb584cd790e2410f436f50632021-11-18T08:00:54ZMorphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.1932-620310.1371/journal.pone.0054040https://doaj.org/article/56f75733eb584cd790e2410f436f50632013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23349783/?tool=EBIhttps://doaj.org/toc/1932-6203Opiates are among the most prescribed drugs for pain management. However, morphine use or abuse results in significant gut bacterial translocation and predisposes patients to serious infections with gut origin. The mechanism underlying this defect is still unknown. In this report, we investigated the mechanisms underlying compromised gut immune function and bacterial translocation following morphine treatment. We demonstrate significant bacterial translocation to mesenteric lymph node (MLN) and liver following morphine treatment in wild-type (WT) animals that was dramatically and significantly attenuated in Toll-like receptor (TLR2 and 4) knockout mice. We further observed significant disruption of tight junction protein organization only in the ileum but not in the colon of morphine treated WT animals. Inhibition of myosin light chain kinase (MLCK) blocked the effects of both morphine and TLR ligands, suggesting the role of MLCK in tight junction modulation by TLR. This study conclusively demonstrates that morphine induced gut epithelial barrier dysfunction and subsequent bacteria translocation are mediated by TLR signaling and thus TLRs can be exploited as potential therapeutic targets for alleviating infections and even sepsis in morphine-using or abusing populations.Jingjing MengHaidong YuJing MaJinghua WangSantanu BanerjeeRick CharboneauRoderick A BarkeSabita RoyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54040 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jingjing Meng Haidong Yu Jing Ma Jinghua Wang Santanu Banerjee Rick Charboneau Roderick A Barke Sabita Roy Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.
description	Opiates are among the most prescribed drugs for pain management. However, morphine use or abuse results in significant gut bacterial translocation and predisposes patients to serious infections with gut origin. The mechanism underlying this defect is still unknown. In this report, we investigated the mechanisms underlying compromised gut immune function and bacterial translocation following morphine treatment. We demonstrate significant bacterial translocation to mesenteric lymph node (MLN) and liver following morphine treatment in wild-type (WT) animals that was dramatically and significantly attenuated in Toll-like receptor (TLR2 and 4) knockout mice. We further observed significant disruption of tight junction protein organization only in the ileum but not in the colon of morphine treated WT animals. Inhibition of myosin light chain kinase (MLCK) blocked the effects of both morphine and TLR ligands, suggesting the role of MLCK in tight junction modulation by TLR. This study conclusively demonstrates that morphine induced gut epithelial barrier dysfunction and subsequent bacteria translocation are mediated by TLR signaling and thus TLRs can be exploited as potential therapeutic targets for alleviating infections and even sepsis in morphine-using or abusing populations.
format	article
author	Jingjing Meng Haidong Yu Jing Ma Jinghua Wang Santanu Banerjee Rick Charboneau Roderick A Barke Sabita Roy
author_facet	Jingjing Meng Haidong Yu Jing Ma Jinghua Wang Santanu Banerjee Rick Charboneau Roderick A Barke Sabita Roy
author_sort	Jingjing Meng
title	Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.
title_short	Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.
title_full	Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.
title_fullStr	Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.
title_full_unstemmed	Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.
title_sort	morphine induces bacterial translocation in mice by compromising intestinal barrier function in a tlr-dependent manner.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/56f75733eb584cd790e2410f436f5063
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Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.

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