Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice
- Author
- Muriel Smet (UGent) , Lien Van Hoecke (UGent) , Ans De Beuckelaer (UGent) , Seppe Vander Beken, Thomas Naessens (UGent) , Karl Vergote (UGent) , Monique Willart (UGent) , Bart Lambrecht (UGent) , Jan-Ake Gustafsson, Knut R Steffensen and Johan Grooten (UGent)
- Organization
- Abstract
- Introduction: Liver X receptors (LXRs) are nuclear receptors that function as cholesterol sensors and regulate cholesterol homeostasis. High cholesterol has been recognized as a risk factor in asthma; however, the mechanism of this linkage is not known. Methods: To explore the importance of cholesterol homeostasis for asthma, we investigated the contribution of LXR activity in an ovalbumin- and a house dust mite-driven eosinophilic asthma mouse model. Results: In both models, airway inflammation, airway hyper-reactivity, and goblet cell hyperplasia were reduced in mice deficient for both LXR and LXR isoforms (LXR-/--/-) as compared to wild-type mice. Inversely, treatment with the LXR agonist GW3965 showed increased eosinophilic airway inflammation. LXR activity contributed to airway inflammation through promotion of type 2 cytokine production as LXR-/--/- mice showed strongly reduced protein levels of IL-5 and IL-13 in the lungs as well as reduced expression of these cytokines by CD4(+) lung cells and lung-draining lymph node cells. In line herewith, LXR activation resulted in increased type 2 cytokine production by the lung-draining lymph node cells. Conclusions: In conclusion, our study demonstrates that the cholesterol regulator LXR acts as a positive regulator of eosinophilic asthma in mice, contributing to airway inflammation through regulation of type 2 cytokine production.
- Keywords
- DIETARY-CHOLESTEROL, EXPRESSION, ATHEROSCLEROSIS, INFLAMMATION, MACROPHAGES, METABOLISM, ACTIVATION, CELLS, MODEL, RISK, asthma, cholesterol, eosinophilic airway inflammation, liver X receptor
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8511422
- MLA
- Smet, Muriel, Lien Van Hoecke, Ans De Beuckelaer, et al. “Cholesterol-sensing Liver X Receptors Stimulate Th2-driven Allergic Eosinophilic Asthma in Mice.” IMMUNITY INFLAMMATION AND DISEASE 4.3 (2016): 350–361. Print.
- APA
- Smet, Muriel, Van Hoecke, L., De Beuckelaer, A., Vander Beken, S., Naessens, T., Vergote, K., Willart, M., et al. (2016). Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice. IMMUNITY INFLAMMATION AND DISEASE, 4(3), 350–361.
- Chicago author-date
- Smet, Muriel, Lien Van Hoecke, Ans De Beuckelaer, Seppe Vander Beken, Thomas Naessens, Karl Vergote, Monique Willart, et al. 2016. “Cholesterol-sensing Liver X Receptors Stimulate Th2-driven Allergic Eosinophilic Asthma in Mice.” Immunity Inflammation and Disease 4 (3): 350–361.
- Chicago author-date (all authors)
- Smet, Muriel, Lien Van Hoecke, Ans De Beuckelaer, Seppe Vander Beken, Thomas Naessens, Karl Vergote, Monique Willart, Bart Lambrecht, Jan-Ake Gustafsson, Knut R Steffensen, and Johan Grooten. 2016. “Cholesterol-sensing Liver X Receptors Stimulate Th2-driven Allergic Eosinophilic Asthma in Mice.” Immunity Inflammation and Disease 4 (3): 350–361.
- Vancouver
- 1.Smet M, Van Hoecke L, De Beuckelaer A, Vander Beken S, Naessens T, Vergote K, et al. Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice. IMMUNITY INFLAMMATION AND DISEASE. 2016;4(3):350–61.
- IEEE
- [1]M. Smet et al., “Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice,” IMMUNITY INFLAMMATION AND DISEASE, vol. 4, no. 3, pp. 350–361, 2016.
@article{8511422,
abstract = {Introduction: Liver X receptors (LXRs) are nuclear receptors that function as cholesterol sensors and regulate cholesterol homeostasis. High cholesterol has been recognized as a risk factor in asthma; however, the mechanism of this linkage is not known.
Methods: To explore the importance of cholesterol homeostasis for asthma, we investigated the contribution of LXR activity in an ovalbumin- and a house dust mite-driven eosinophilic asthma mouse model.
Results: In both models, airway inflammation, airway hyper-reactivity, and goblet cell hyperplasia were reduced in mice deficient for both LXR and LXR isoforms (LXR-/--/-) as compared to wild-type mice. Inversely, treatment with the LXR agonist GW3965 showed increased eosinophilic airway inflammation. LXR activity contributed to airway inflammation through promotion of type 2 cytokine production as LXR-/--/- mice showed strongly reduced protein levels of IL-5 and IL-13 in the lungs as well as reduced expression of these cytokines by CD4(+) lung cells and lung-draining lymph node cells. In line herewith, LXR activation resulted in increased type 2 cytokine production by the lung-draining lymph node cells.
Conclusions: In conclusion, our study demonstrates that the cholesterol regulator LXR acts as a positive regulator of eosinophilic asthma in mice, contributing to airway inflammation through regulation of type 2 cytokine production.},
author = {Smet, Muriel and Van Hoecke, Lien and De Beuckelaer, Ans and Vander Beken, Seppe and Naessens, Thomas and Vergote, Karl and Willart, Monique and Lambrecht, Bart and Gustafsson, Jan-Ake and Steffensen, Knut R and Grooten, Johan},
issn = {2050-4527},
journal = {IMMUNITY INFLAMMATION AND DISEASE},
keywords = {DIETARY-CHOLESTEROL,EXPRESSION,ATHEROSCLEROSIS,INFLAMMATION,MACROPHAGES,METABOLISM,ACTIVATION,CELLS,MODEL,RISK,asthma,cholesterol,eosinophilic airway inflammation,liver X receptor},
language = {eng},
number = {3},
pages = {350--361},
title = {Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice},
url = {http://dx.doi.org/10.1002/iid3.118},
volume = {4},
year = {2016},
}
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