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Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1

Leen Puimège (UGent) , Filip Van Hauwermeiren (UGent) , Sophie Steeland (UGent) , Sara Van Ryckeghem (UGent) , Jolien Vandewalle (UGent) , Sofie Lodens (UGent) , Lien Dejager (UGent) , Sofie Vandevyver (UGent) , Jan Staelens, Steven Timmermans (UGent) , et al.
(2015) EMBO MOLECULAR MEDICINE. 7(8). p.1004-1017
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Abstract
TNF is a central actor during inflammation and a well-recognized drug target for inflammatory diseases. We found that the mouse strain SPRET/Ei, known for extreme and dominant resistance against TNF-induced shock, displays weak expression of TNF receptor 1 protein (TNFR1) but normal mRNA expression, a trait genetically linked to the major TNFR1 coding gene Tnfrsf1a and to a locus harbouring the predicted TNFR1-regulating miR-511. This miRNA is a genuine TNFR1 regulator in cells. In mice, overexpression of miR-511 down-regulates TNFR1 and protects against TNF, while anti-miR-511 up-regulates TNFR1 and sensitizes for TNF, breaking the resistance of SPRET/Ei. We found that miR-511 inhibits endotoxemia and experimental hepatitis and that this miR is strongly induced by glucocorticoids and is a true TNFR1 modulator and thus an anti-inflammatory miR. Since minimal reductions of TNFR1 have considerable effects on TNF sensitivity, we believe that at least part of the anti-inflammatory effects of glucocorti-coids are mediated by induction of this miR, resulting in reduced TNFR1 expression.
Keywords
glucocorticoids, miRs, receptor regulation, sepsis, TNF, TUMOR-NECROSIS-FACTOR, SPRET/EI MICE, RECEPTOR DIMERIZATION, GENE-EXPRESSION, LPS RESISTANCE, LETHAL SHOCK, CELLS, IDENTIFICATION, MACROPHAGES, PROMOTER

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Citation

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Chicago
Puimège, Leen, Filip Van Hauwermeiren, Sophie Steeland, Sara Van Ryckeghem, Jolien Vandewalle, Sofie Lodens, Lien Dejager, et al. 2015. “Glucocorticoid-induced microRNA-511 Protects Against TNF by Down-regulating TNFR1.” Embo Molecular Medicine 7 (8): 1004–1017.
APA
Puimège, L., Van Hauwermeiren, F., Steeland, S., Van Ryckeghem, S., Vandewalle, J., Lodens, S., Dejager, L., et al. (2015). Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1. EMBO MOLECULAR MEDICINE, 7(8), 1004–1017.
Vancouver
1.
Puimège L, Van Hauwermeiren F, Steeland S, Van Ryckeghem S, Vandewalle J, Lodens S, et al. Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1. EMBO MOLECULAR MEDICINE. 2015;7(8):1004–17.
MLA
Puimège, Leen, Filip Van Hauwermeiren, Sophie Steeland, et al. “Glucocorticoid-induced microRNA-511 Protects Against TNF by Down-regulating TNFR1.” EMBO MOLECULAR MEDICINE 7.8 (2015): 1004–1017. Print.
@article{6970716,
  abstract     = {TNF is a central actor during inflammation and a well-recognized drug target for inflammatory diseases. We found that the mouse strain SPRET/Ei, known for extreme and dominant resistance against TNF-induced shock, displays weak expression of TNF receptor 1 protein (TNFR1) but normal mRNA expression, a trait genetically linked to the major TNFR1 coding gene Tnfrsf1a and to a locus harbouring the predicted TNFR1-regulating miR-511. This miRNA is a genuine TNFR1 regulator in cells. In mice, overexpression of miR-511 down-regulates TNFR1 and protects against TNF, while anti-miR-511 up-regulates TNFR1 and sensitizes for TNF, breaking the resistance of SPRET/Ei. We found that miR-511 inhibits endotoxemia and experimental hepatitis and that this miR is strongly induced by glucocorticoids and is a true TNFR1 modulator and thus an anti-inflammatory miR. Since minimal reductions of TNFR1 have considerable effects on TNF sensitivity, we believe that at least part of the anti-inflammatory effects of glucocorti-coids are mediated by induction of this miR, resulting in reduced TNFR1 expression.},
  author       = {Puim{\`e}ge, Leen and Van Hauwermeiren, Filip and Steeland, Sophie and Van Ryckeghem, Sara and Vandewalle, Jolien and Lodens, Sofie and Dejager, Lien and Vandevyver, Sofie and Staelens, Jan and Timmermans, Steven and Vandenbroucke, Roosmarijn and Libert, Claude},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {glucocorticoids,miRs,receptor regulation,sepsis,TNF,TUMOR-NECROSIS-FACTOR,SPRET/EI MICE,RECEPTOR DIMERIZATION,GENE-EXPRESSION,LPS RESISTANCE,LETHAL SHOCK,CELLS,IDENTIFICATION,MACROPHAGES,PROMOTER},
  language     = {eng},
  number       = {8},
  pages        = {1004--1017},
  title        = {Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1},
  url          = {http://dx.doi.org/10.15252/emmm.201405010},
  volume       = {7},
  year         = {2015},
}

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