Morphine induced exacerbation of sepsis is mediated by tempering endotoxin tolerance through modulation of miR-146a

被引：61

作者：

Banerjee, Santanu ^{[1
]}

Meng, Jingjing ^{[2
]}

Das, Subhas ^{[1
]}

Krishnan, Anitha ^{[1
]}

Haworth, Justin ^{[1
]}

Charboneau, Richard ^{[3
]}

Zeng, Yan ^{[2
]}

Ramakrishnan, Sundaram ^{[2
]}

Roy, Sabita ^{[1
,2
]}

机构：

[1] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA

[3] Vet Affairs Med Ctr, Minneapolis, MN 55417 USA

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

关键词：

PATTERN-RECOGNITION RECEPTORS; INNATE IMMUNITY; MICRORNAS; LIPOPOLYSACCHARIDE; EXPRESSION; MECHANISMS; SUSCEPTIBILITY; INFLAMMATION; REPRESSION; INDUCTION;

D O I：

10.1038/srep01977

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Development of tolerance to endotoxin prevents sustained hyper inflammation during systemic infections. Here we report for the first time that chronic morphine treatment tempers endotoxin tolerance resulting in persistent inflammation, septicemia and septic shock. Morphine was found to down-regulate endotoxin/LPS induced miR-146a and 155 in macrophages. However, only miR-146a over expression, but not miR-155 abrogates morphine mediated hyper-inflammation. Conversely, antagonizing miR-146a (but not miR-155) heightened the severity of morphine-mediated hyper-inflammation. These results suggest that miR-146a acts as a molecular switch controlling hyper-inflammation in clinical and/or recreational use of morphine.

引用

页数：12

共 55 条

[1]

Pathogen recognition and innate immunity [J].

Akira, S ;

Uematsu, S ;

Takeuchi, O .

CELL, 2006, 124 (04) :783-801

[2]

The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs [J].

Androulidaki, Ariadne ;

Iliopoulos, Dimitrios ;

Arranz, Alicia ;

Doxaki, Christina ;

Schworer, Steffen ;

Zacharioudaki, Vassiliki ;

Margioris, Andrew N. ;

Tsichlis, Philip N. ;

Tsatsanis, Christos .

IMMUNITY, 2009, 31 (02) :220-231

[3]

Pseudomonas aeruginosa Virulence Expression Is Directly Activated by Morphine and Is Capable of Causing Lethal Gut-Derived Sepsis in Mice During Chronic Morphine Administration [J].

Babrowski, Trissa ;

Holbrook, Christopher ;

Moss, Jonathan ;

Gottlieb, Lawrence ;

Valuckaite, Vesta ;

Zaborin, Alexander ;

Poroyko, Valeriy ;

Liu, Donald C. ;

Zaborina, Olga ;

Alverdy, John C. .

ANNALS OF SURGERY, 2012, 255 (02) :386-393

[4]

MicroRNAs and LPS: Developing a Relationship in the Neonatal Gut [J].

Barbalat, Roman ;

Barton, Gregory M. .

CELL HOST & MICROBE, 2010, 8 (04) :303-304

[5]

MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].

Bartel, David P. .

CELL, 2007, 131 (04) :11-29

[6]

Endotoxin tolerance: new mechanisms, molecules and clinical significance [J].

Biswas, Subhra K. ;

Lopez-Collazo, Eduardo .

TRENDS IN IMMUNOLOGY, 2009, 30 (10) :475-487

[7]

Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is μ-opioid receptor-dependent [J].

Breslow, Jessica M. ;

Feng, Pu ;

Meissler, Joseph J. ;

Pintar, John E. ;

Gaughan, John ;

Adler, Martin W. ;

Eisenstein, Toby K. .

MICROBIAL PATHOGENESIS, 2010, 49 (06) :330-335

[8]

Downregulation of miR-27a*and miR-532-5p and Upregulation of miR-146a and miR-155 in LPS-induced RAW264.7 Macrophage Cells [J].

Cheng, Ying ;

Kuang, Wenhua ;

Hao, Yongchang ;

Zhang, Donglin ;

Lei, Ming ;

Du, Li ;

Jiao, Hanwei ;

Zhang, Xiaoru ;

Wang, Fengyang .

INFLAMMATION, 2012, 35 (04) :1308-1313

[9]

Morphine Modulation of Toll-Like Receptors in Microglial Cells Potentiates Neuropathogenesis in a HIV-1 Model of Coinfection with Pneumococcal Pneumoniae [J].

Dutta, Raini ;

Krishnan, Anitha ;

Meng, Jingjing ;

Das, Subash ;

Ma, Jing ;

Banerjee, Santanu ;

Wang, Jinghua ;

Charboneau, Richard ;

Prakash, Om ;

Barke, Roderick A. ;

Roy, Sabita .

JOURNAL OF NEUROSCIENCE, 2012, 32 (29) :9917-9930

[10]

MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming [J].

El Gazzar, Mohamed ;

Church, Ashley ;

Liu, Tiefu ;

McCall, Charles E. .

JOURNAL OF LEUKOCYTE BIOLOGY, 2011, 90 (03) :509-519

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