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

被引：55

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：

07 ; 0710 ; 09 ;

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

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