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Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1

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Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. / Vettorazzi, Sabine; Bode, Constantin; Dejager, Lien; Frappart, Lucien; Shelest, Ekaterina; Klaßen, Carina; Tasdogan, Alpaslan; Reichardt, Holger M; Libert, Claude; Schneider, Marion; Weih, Falk; Henriette Uhlenhaut, N; David, Jean-Pierre; Gräler, Markus; Kleiman, Anna; Tuckermann, Jan P.

In: NAT COMMUN, Vol. 6, 2015, p. 7796.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vettorazzi, S, Bode, C, Dejager, L, Frappart, L, Shelest, E, Klaßen, C, Tasdogan, A, Reichardt, HM, Libert, C, Schneider, M, Weih, F, Henriette Uhlenhaut, N, David, J-P, Gräler, M, Kleiman, A & Tuckermann, JP 2015, 'Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1', NAT COMMUN, vol. 6, pp. 7796. https://doi.org/10.1038/ncomms8796

APA

Vettorazzi, S., Bode, C., Dejager, L., Frappart, L., Shelest, E., Klaßen, C., Tasdogan, A., Reichardt, H. M., Libert, C., Schneider, M., Weih, F., Henriette Uhlenhaut, N., David, J-P., Gräler, M., Kleiman, A., & Tuckermann, J. P. (2015). Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. NAT COMMUN, 6, 7796. https://doi.org/10.1038/ncomms8796

Vancouver

Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, Klaßen C et al. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. NAT COMMUN. 2015;6:7796. https://doi.org/10.1038/ncomms8796

Bibtex

@article{c44745209e4f494aaf3d92ceb8ce0550,
title = "Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1",
abstract = "Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies.",
author = "Sabine Vettorazzi and Constantin Bode and Lien Dejager and Lucien Frappart and Ekaterina Shelest and Carina Kla{\ss}en and Alpaslan Tasdogan and Reichardt, {Holger M} and Claude Libert and Marion Schneider and Falk Weih and {Henriette Uhlenhaut}, N and Jean-Pierre David and Markus Gr{\"a}ler and Anna Kleiman and Tuckermann, {Jan P}",
year = "2015",
doi = "10.1038/ncomms8796",
language = "English",
volume = "6",
pages = "7796",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1

AU - Vettorazzi, Sabine

AU - Bode, Constantin

AU - Dejager, Lien

AU - Frappart, Lucien

AU - Shelest, Ekaterina

AU - Klaßen, Carina

AU - Tasdogan, Alpaslan

AU - Reichardt, Holger M

AU - Libert, Claude

AU - Schneider, Marion

AU - Weih, Falk

AU - Henriette Uhlenhaut, N

AU - David, Jean-Pierre

AU - Gräler, Markus

AU - Kleiman, Anna

AU - Tuckermann, Jan P

PY - 2015

Y1 - 2015

N2 - Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies.

AB - Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies.

U2 - 10.1038/ncomms8796

DO - 10.1038/ncomms8796

M3 - SCORING: Journal article

C2 - 26183376

VL - 6

SP - 7796

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -