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

Santanu Banerjee; Jingjing Meng; Subhas Das; Anitha Krishnan; Justin Haworth; Richard Charboneau; Yan Zeng; Sundaram Ramakrishnan; Sabita Roy

doi:10.1038/srep01977

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

Santanu Banerjee, Jingjing Meng, Subhas Das, Anitha Krishnan, Justin Haworth, Richard Charboneau, Yan Zeng, Sundaram Ramakrishnan, Sabita Roy

Biochemistry & Microbiology

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Abstract

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.

Original language	English
Article number	1977
Journal	Scientific Reports
Volume	3
DOIs	https://doi.org/10.1038/srep01977
State	Published - 2013

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

abstract = "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.",

author = "Santanu Banerjee and Jingjing Meng and Subhas Das and Anitha Krishnan and Justin Haworth and Richard Charboneau and Yan Zeng and Sundaram Ramakrishnan and Sabita Roy",

note = "Funding Information: This work was supported in part by the NIH grants RO1 DA 12104, RO1 DA 022935, RO1 DA031202, K05DA033881, P50 DA 011806 and 1R01DA034582 to SRoy.",

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T1 - Morphine induced exacerbation of sepsis is mediated by tempering endotoxin tolerance through modulation of miR-146a

AU - Banerjee, Santanu

AU - Meng, Jingjing

AU - Das, Subhas

AU - Krishnan, Anitha

AU - Haworth, Justin

AU - Charboneau, Richard

AU - Zeng, Yan

AU - Ramakrishnan, Sundaram

AU - Roy, Sabita

N1 - Funding Information: This work was supported in part by the NIH grants RO1 DA 12104, RO1 DA 022935, RO1 DA031202, K05DA033881, P50 DA 011806 and 1R01DA034582 to SRoy.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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

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