The roles of liver X receptor α in inflammation and inflammation-associated diseases.
LXRs agonists
LXRα
cholesterol homeostasis
inflammation
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
19
10
2020
received:
20
06
2020
accepted:
24
11
2020
pubmed:
12
12
2020
medline:
15
10
2021
entrez:
11
12
2020
Statut:
ppublish
Résumé
Liver X receptor α (LXRα; also known as NR1H3), an isoform of LXRs, is a member of the nuclear receptor family of transcription factors and plays essential roles in the transcriptional control of cholesterol homeostasis. Previous in-depth phenotypic analyses of mouse models with deficient LXRα have also demonstrated various physiological functions of this receptor within inflammatory responses. LXRα activation exerts a combination of metabolic and anti-inflammatory actions resulting in the modulation and the amelioration of inflammatory disorders. The tight "repercussions" between LXRα and inflammation, as well as cholesterol homeostasis, have suggested that LXRα could be pharmacologically targeted in pathologies such as atherosclerosis, acute lung injury, and Alzheimer's disease. This review gives an overview of the recent advances in understanding the roles of LXRα in inflammation and inflammation-associated diseases, which will help in the design of future experimental researches on the potential of LXRα and advance the investigation of LXRα as pharmacological inflammatory targets.
Substances chimiques
Liver X Receptors
0
NR1H2 protein, human
0
NR1H3 protein, human
0
Nr1h2 protein, mouse
0
Nr1h3 protein, mouse
0
Protein Isoforms
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4807-4828Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Ahn, S. B., Jang, K., Jun, D. W., Lee, B. H., & Shin, K. J. (2014). Expression of liver X receptor correlates with intrahepatic inflammation and fibrosis in patients with nonalcoholic fatty liver disease. Digestive Diseases and Sciences, 59(12), 2975-2982. https://doi.org/10.1007/s10620-014-3289-x
Anthonisen, E. H., Berven, L., Holm, S., Nygård, M., Nebb, H. I., & Grønning-Wang, L. M. (2010). Nuclear receptor liver X receptor is O-GlcNAc-modified in response to glucose. The Journal of Biological Chemistry, 285(3), 1607-1615. https://doi.org/10.1074/jbc.M109.082685
Apfel, R., Benbrook, D., Lernhardt, E., Ortiz, M. A., Salbert, G., & Pfahl, M. (1994). A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Molecular and Cellular Biology, 14(10), 7025-7035. https://doi.org/10.1128/mcb.14.10.7025
Baudoin, L., & Issad, T. (2014). O-GlcNAcylation and inflammation: A vast territory to explore. Frontiers in Endocrinology, 5, 235. https://doi.org/10.3389/fendo.2014.00235
Becares, N., Gage, M. C., Voisin, M., Shrestha, E., Martin-Gutierrez, L., Liang, N., Louie, R., Pourcet, B., Pello, O. M., Luong, T. V., Goni, S., Pichardo-Almarza, C., Roberg-Larsen, H., Diaz-Zuccarini, V., Steffensen, K. R., O'Brien, A., Garabedian, M. J., Rombouts, K., Treuter, E., & Pineda-Torra, I. (2019). Impaired LXRalpha phosphorylation attenuates progression of fatty liver disease. Cell Reports, 26(4), 984-995. https://doi.org/10.1016/j.celrep.2018.12.094
Benoit, G., Cooney, A., Giguere, V., Ingraham, H., Lazar, M., Muscat, G., Perlmann, T., Renaud, J. P., Schwabe, J., Sladek, F., Tsai, M. J., & Laudet, V. (2006). International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacological Reviews, 58(4), 798-836. https://doi.org/10.1124/pr.58.4.10
Birrell, M. A., De Alba, J., Catley, M. C., Hardaker, E., Wong, S., Collins, M., Clarke, D. L., Farrow, S. N., Willson, T. M., Collins, J. L., & Belvisi, M. G. (2008). Liver X receptor agonists increase airway reactivity in a model of asthma via increasing airway smooth muscle growth, Journal of immunology (Baltimore, Md: 1950) 181(6), pp. 4265-4271. https://doi.org/10.4049/jimmunol.181.6.4265
Bischoff, E. D., Daige, C. L., Petrowski, M., Dedman, H., Pattison, J., Juliano, J., Li, A. C., & Schulman, I. G. (2010). Non-redundant roles for LXRalpha and LXRbeta in atherosclerosis susceptibility in low density lipoprotein receptor knockout mice. Journal of Lipid Research, 51(5), 900-906. https://doi.org/10.1194/jlr.M900096
Blaschke, F., Leppanen, O., Takata, Y., Caglayan, E., Liu, J., Fishbein, M. C., Kappert, K., Nakayama, K. I., Collins, A. R., Fleck, E., Hsueh, W. A., Law, R. E., & Bruemmer, D. (2004). Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circulation Research, 95(12), e110-e123. https://doi.org/10.1161/01.RES.0000150368.56660.4f
Botez, G., Piraino, G., Hake, P. W., Ledford, J. R., O'Connor, M., Cook, J. A., & Zingarelli, B. (2015). Age-dependent therapeutic effects of liver X receptor-α activation in murine polymicrobial sepsis. Innate Immunity, 21(6), 609-618. https://doi.org/10.1177/1753425915569367
Calkin, A. C., & Tontonoz, P. (2010). Liver x receptor signaling pathways and atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(8), 1513-1518. https://doi.org/10.1161/atvbaha.109.191197
Cao, G., Bales, K. R., DeMattos, R. B., & Paul, S. M. (2007). Liver X receptor-mediated gene regulation and cholesterol homeostasis in brain: Relevance to Alzheimer's disease therapeutics. Current Alzheimer Research, 4(2), 179-184. https://doi.org/10.2174/156720507780362173
Cao, Q., Wang, X., Jia, L., Mondal, A. K., Diallo, A., Hawkins, G. A., Das, S. K., Parks, J. S., Yu, L., Shi, H., Shi, H., & Xue, B. (2014). Inhibiting DNA methylation by 5-Aza-2'-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation. Endocrinology, 155(12), 4925-4938. https://doi.org/10.1210/en.2014-1595
Catapano, A. L., Pirillo, A., & Norata, G. D. (2017). Vascular inflammation and low-density lipoproteins: Is cholesterol the link? A lesson from the clinical trials. British Journal of Pharmacology, 174(22), 3973-3985. https://doi.org/10.1111/bph.13805
Chawla, A., Repa, J. J., Evans, R. M., & Mangelsdorf, D. J. (2001). Nuclear receptors and lipid physiology: Opening the X-files. Science (New York, NY), 294(5548), 1866-1870. https://doi.org/10.1126/science.294.5548.1866
Chen, M., Bradley, M. N., Beaven, S. W., & Tontonoz, P. (2006). Phosphorylation of the liver X receptors. FEBS Letters, 580(20), 4835-4841. https://doi.org/10.1016/j.febslet.2006.07.074
Courtney, R., & Landreth, G. E. (2016). LXR regulation of brain cholesterol: From development to disease. Trends in Endocrinology and Metabolism, 27(6), 404-414. https://doi.org/10.1016/j.tem.2016.03.018
Cramer, P. E., Cirrito, J. R., Wesson, D. W., Lee, C. Y., Karlo, J. C., Zinn, A. E., Casali, B. T., Restivo, J. L., Goebel, W. D., James, M. J., Brunden, K. R., Wilson, D. A., & Landreth, G. E. (2012). ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science (New York, NY), 335(6075), 1503-1506. https://doi.org/10.1126/science.1217697
Dela Justina, V., Gonçalves, J. S., de Freitas, R. A., Fonseca, A. D., Volpato, G. T., Tostes, R. C., Carneiro, F. S., Lima, V. V., & Giachini, F. R. (2017). Increased O-linked N-acetylglucosamine modification of NF-ΚB and augmented cytokine production in the placentas from hyperglycemic rats. Inflammation, 40(5), 1773-1781. https://doi.org/10.1007/s10753-017-0620-7
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte chemoattractant protein-1 (MCP-1): An overview. Journal of Interferon & Cytokine Research, 29(6), 313-326. https://doi.org/10.1089/jir.2008.0027
Ding, H., Li, Y., Feng, Y., Chen, J., Zhong, X., Wang, N., Wang, W., Zhang, P., & Wang, L. (2016). LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factorkappaB. Molecular Medicine Reports, 13(6), 4888-4896. https://doi.org/10.3892/mmr.2016.5138
Du, C., Shi, Y., Ren, Y., Wu, H., Yao, F., Wei, J., Wu, M., Hou, Y., & Duan, H. (2015). Anthocyanins inhibit high-glucose-induced cholesterol accumulation and inflammation by activating LXRalpha pathway in HK-2 cells. Drug Design, Development and Therapy, 9, 5099-5113. https://doi.org/10.2147/dddt.s90201
Endo-Umeda, K., Aoyama, A., Shimizu, M., Ishikawa, M., Hashimoto, Y., Yamada, S., & Makishima, M. (2017). 1alpha-Hydroxy derivatives of 7-dehydrocholesterol are selective liver X receptor modulators. The Journal of Steroid Biochemistry and Molecular Biology, 172, 136-148. https://doi.org/10.1016/j.jsbmb.2017.07.014
Fan, Q., Moen, A., Anonsen, J. H., Bindesbøll, C., Saether, T., Carlson, C. R., & Grønning-Wang, L. M. (2018). O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase. Biochemical and Biophysical Research Communications, 499(2), 354-360. https://doi.org/10.1016/j.bbrc.2018.03.164
Fan, X., Kim, H. J., Bouton, D., Warner, M., & Gustafsson, J. A. (2008). Expression of liver X receptor beta is essential for formation of superficial cortical layers and migration of later-born neurons. Proceedings of the National Academy of Sciences of the United States of America, 105(36), 13445-13450. https://doi.org/10.1073/pnas.0806974105
Faulds, M. H., Zhao, C., & Dahlman-Wright, K. (2010). Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases. Current Opinion in Pharmacology, 10(6), 692-697. https://doi.org/10.1016/j.coph.2010.07.003
Fontaine, C., Rigamonti, E., Nohara, A., Gervois, P., Teissier, E., Fruchart, J. C., Staels, B., & Chinetti-Gbaguidi, G. (2007). Liver X receptor activation potentiates the lipopolysaccharide response in human macrophages. Circulation Research, 101(1), 40-49. https://doi.org/10.1161/circresaha.106.135814
Fontaine, C., Rigamonti, E., Pourcet, B., Duez, H., Duhem, C., Fruchart, J. C., Chinetti-Gbaguidi, G., & Staels, B. (2008). The nuclear receptor Rev-erbalpha is a liver X receptor (LXR) target gene driving a negative feedback loop on select LXR-induced pathways in human macrophages. Molecular Endocrinology (Baltimore, Md), 22(8), 1797-1811. https://doi.org/10.1210/me.2007-0439
Fu, Y., Wei, Z., Zhou, E., Zhang, N., & Yang, Z. (2014). Cyanidin-3-O-beta-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model. Journal of Lipid Research, 55(6), 1111-1119. https://doi.org/10.1194/jlr.M047340
Fu, Y., Xin, Z., Liu, B., Wang, J., Wang, J., Zhang, X., Wang, Y., & Li, F. (2017). Platycodin D inhibits inflammatory response in LPS-stimulated primary rat microglia cells through activating LXRalpha-ABCA1 signaling pathway. Frontiers in Immunology, 8, 1929. https://doi.org/10.3389/fimmu.2017.01929
Gabbi, C., Warner, M., & Gustafsson, J. A. (2009). Minireview: Liver X receptor beta: Emerging roles in physiology and diseases. Molecular Endocrinology (Baltimore, Md), 23(2), 129-136. https://doi.org/10.1210/me.2008-0398
Gage, M. C., Becares, N., Louie, R., Waddington, K. E., Zhang, Y., Tittanegro, T. H., Rodriguez-Lorenzo, S., Jathanna, A., Pourcet, B., Pello, O. M., De la Rosa, J. V., Castrillo, A., & Pineda-Torra, I. (2018). Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation. Proceedings of the National Academy of Sciences of the United States of America, 115(28), E6556-e6565. https://doi.org/10.1073/pnas.1721245115
Gerin, I., Dolinsky, V. W., Shackman, J. G., Kennedy, R. T., Chiang, S. H., Burant, C. F., Steffensen, K. R., Gustafsson, J. A., & MacDougald, O. A. (2005). LXRbeta is required for adipocyte growth, glucose homeostasis, and beta cell function. The Journal of Biological Chemistry, 280(24), 23024-23031. https://doi.org/10.1074/jbc.M412564200
Ghisletti, S., Huang, W., Ogawa, S., Pascual, G., Lin, M. E., Willson, T. M., Rosenfeld, M. G., & Glass, C. K. (2007). Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Molecular Cell, 25(1), 57-70. https://doi.org/10.1016/j.molcel.2006.11.022
Grebe, A., Hoss, F., & Latz, E. (2018). NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circulation Research, 122(12), 1722-1740. https://doi.org/10.1161/circresaha.118.311362
Groves, J. T., & Wang, C. C. (2000). Nitric oxide synthase: Models and mechanisms. Current Opinion in Chemical Biology, 4(6), 687-695. https://doi.org/10.1016/s1367-5931(00)00146-0
He, K., Dai, Z. Y., Li, P. Z., Zhu, X. W., & Gong, J. P. (2015). Association between liver X receptor-α and neuron-derived orphan nuclear receptor-1 in Kupffer cells of C57BL/6 mice during inflammation. Molecular Medicine Reports, 12(4), 6098-6104. https://doi.org/10.3892/mmr.2015.4155
He, Q., Pu, J., Yuan, A., Lau, W. B., Gao, E., Koch, W. J., Ma, X. L., & He, B. (2014). Activation of liver-X-receptor alpha but not liver-X-receptor beta protects against myocardial ischemia/reperfusion injury. Circulation Heart failure, 7(6), 1032-1041. https://doi.org/10.1161/circheartfailure.114.001260
Hong, C., Bradley, M. N., Rong, X., Wang, X., Wagner, A., Grijalva, V., Castellani, L. W., Salazar, J., Realegeno, S., Boyadjian, R., Fogelman, A. M., Van Lenten, B. J., Reddy, S. T., Lusis, A. J., Tangirala, R. K., & Tontonoz, P. (2012). LXRalpha is uniquely required for maximal reverse cholesterol transport and atheroprotection in ApoE-deficient mice. Journal of Lipid Research, 53(6), 1126-1133. https://doi.org/10.1194/jlr.M022061
Hu, X., Steffensen, K. R., Jiang, Z. Y., Parini, P., Gustafsson, J. A., Gafvels, M., & Eggertsen, G. (2012). LXRbeta activation increases intestinal cholesterol absorption, leading to an atherogenic lipoprotein profile. Journal of Internal Medicine, 272(5), 452-464. https://doi.org/10.1111/j.1365-2796.2012.02529.x
Hu, X., Fu, Y., Lu, X., Zhang, Z., Zhang, W., Cao, Y., & Zhang, N. (2016). Protective effects of platycodin D on lipopolysaccharide-induced acute lung injury by activating LXRalpha-ABCA1 signaling pathway. Frontiers in Immunology, 7, 644. https://doi.org/10.3389/fimmu.2016.00644
Huang, N., Shaik-Dasthagirisaheb, Y. B., LaValley, M. P., Gibson, F. C., 3rd (2015). Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss. Molecular Oral Microbiology, 30(6), 438-450. https://doi.org/10.1111/omi.12103
Hwahng, S. H., Ki, S. H., Bae, E. J., Kim, H. E., & Kim, S. G. (2009). Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones. Hepatology, 49(6), 1913-1925. https://doi.org/10.1002/hep.22887
Ishibashi, M., Filomenko, R., Rébé, C., Chevriaux, A., Varin, A., Derangère, V., Bessède, G., Gambert, P., Lagrost, L., & Masson, D. (2013a). Knock-down of the oxysterol receptor LXRα impairs cholesterol efflux in human primary macrophages: Lack of compensation by LXRβ activation. Biochemical Pharmacology, 86(1), 122-129. https://doi.org/10.1016/j.bcp.2012.12.024
Ishibashi, M., Filomenko, R., Rebe, C., Chevriaux, A., Varin, A., Derangere, V., Bessede, G., Gambert, P., Lagrost, L., & Masson, D. (2013b). Knock-down of the oxysterol receptor LXRalpha impairs cholesterol efflux in human primary macrophages: Lack of compensation by LXRbeta activation. Biochemical Pharmacology, 86(1), 122-129. https://doi.org/10.1016/j.bcp.2012.12.024
Ito, A., Hong, C., Rong, X., Zhu, X., Tarling, E. J., Hedde, P. N., Gratton, E., Parks, J., & Tontonoz, P. (2015). LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. eLife, 4, e08009. https://doi.org/10.7554/eLife.08009
Janowski, B. A., Willy, P. J., Devi, T. R., Falck, J. R., & Mangelsdorf, D. J. (1996). An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature, 383(6602), 728-731. https://doi.org/10.1038/383728a0
Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., & Tontonoz, P. (2003). Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nature Medicine, 9(2), 213-219. https://doi.org/10.1038/nm820
Kalaany, N. Y., & Mangelsdorf, D. J. (2006). LXRS and FXR: The yin and yang of cholesterol and fat metabolism. Annual Review of Physiology, 68, 159-191. https://doi.org/10.1146/annurev.physiol.68.033104.152158
Katz, A., Udata, C., Ott, E., Hickey, L., Burczynski, M. E., Burghart, P., Vesterqvist, O., & Meng, X. (2009). Safety, pharmacokinetics, and pharmacodynamics of single doses of LXR-623, a novel liver X-receptor agonist, in healthy participants. Journal of Clinical Pharmacology, 49(6), 643-649. https://doi.org/10.1177/0091270009335768
Kim, H. Y., Cho, H. K., Kim, H. H., & Cheong, J. (2011). Oxygenated derivatives of cholesterol promote hepatitis B virus gene expression through nuclear receptor LXRalpha activation. Virus Research, 158(1-2), 55-61. https://doi.org/10.1016/j.virusres.2011.03.010
Kim, S. Y., Lim, E. J., Yoon, Y. S., Ahn, Y. H., Park, E. M., Kim, H. S., & Kang, J. L. (2016). Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages. Scientific Reports, 6, 29673. https://doi.org/10.1038/srep29673
Kumar, N., Wang, H., Liu, D., & Collins, S. (2009). Liver X receptor is a regulator of orphan nuclear receptor NOR-1 gene transcription in adipocytes. International Journal of Obesity (2005), 33(5), 519-524. https://doi.org/10.1038/ijo.2009.32
Laffitte, B. A., Repa, J. J., Joseph, S. B., Wilpitz, D. C., Kast, H. R., Mangelsdorf, D. J., & Tontonoz, P. (2001). LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proceedings of the National Academy of Sciences of the United States of America, 98(2), 507-512. https://doi.org/10.1073/pnas.021488798
Lee, J. H., Kim, H., Park, S. J., Woo, J. H., Joe, E. H., & Jou, I. (2016). Small heterodimer partner SHP mediates liver X receptor (LXR)-dependent suppression of inflammatory signaling by promoting LXR SUMOylation specifically in astrocytes. Science Signaling, 9(439), ra78. https://doi.org/10.1126/scisignal.aaf4850
Lee, J. H., Park, S. M., Kim, O. S., Lee, C. S., Woo, J. H., Park, S. J., Joe, E. H., & Jou, I. (2009). Differential SUMOylation of LXRalpha and LXRbeta mediates transrepression of STAT1 inflammatory signaling in IFN-gamma-stimulated brain astrocytes. Molecular Cell, 35(6), 806-817. https://doi.org/10.1016/j.molcel.2009.07.021
Lehmann, J. M., Kliewer, S. A., Moore, L. B., Smith-Oliver, T. A., Oliver, B. B., Su, J. L., Sundseth, S. S., Winegar, D. A., Blanchard, D. E., Spencer, T. A., & Willson, T. M. (1997). Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. The Journal of Biological Chemistry, 272(6), 3137-3140. https://doi.org/10.1074/jbc.272.6.3137
Lei, C., Lin, R., Wang, J., Tao, L., Fu, X., Qiu, Y., & Lei, B. (2017). Amelioration of amyloid beta-induced retinal inflammatory responses by a LXR agonist TO901317 is associated with inhibition of the NF-kappaB signaling and NLRP3 inflammasome. Neuroscience, 360, 48-60. https://doi.org/10.1016/j.neuroscience.2017.07.053
Lei, P., Baysa, A., Nebb, H. I., Valen, G., Skomedal, T., Osnes, J. B., Yang, Z., & Haugen, F. (2013). Activation of Liver X receptors in the heart leads to accumulation of intracellular lipids and attenuation of ischemia-reperfusion injury. Basic Research in Cardiology, 108(1), 323. https://doi.org/10.1007/s00395-012-0323-z
Lewis, B. A., & Hanover, J. A. (2014). O-GlcNAc and the epigenetic regulation of gene expression. The Journal of Biological Chemistry, 289(50), 34440-34448. https://doi.org/10.1074/jbc.R114.595439
Li, P., Wang, G., Zhang, X. L., He, G. L., Luo, X., Yang, J., Luo, Z., Shen, T. T., & Yang, X. S. (2019). MicroRNA-155 promotes heat stress-induced inflammation via targeting liver X receptor alpha in Microglia. Frontiers in Cellular Neuroscience, 13, 12. https://doi.org/10.3389/fncel.2019.00012
Li, X., Yeh, V., & Molteni, V. (2010). Liver X receptor modulators: A review of recently patented compounds (2007-2009). Expert Opinion on Therapeutic Patents, 20(4), 535-562. https://doi.org/10.1517/13543771003621269
Li, X., Zhang, S., Blander, G., Tse, J. G., Krieger, M., & Guarente, L. (2007). SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Molecular Cell, 28(1), 91-106. https://doi.org/10.1016/j.molcel.2007.07.032
Li, Y., Zhang, X. S., & Yu, J. L. (2016). Acanthoic acid inhibits LPS-induced inflammatory response by activating LXRalpha in human umbilical vein endothelial cells. International Immunopharmacology, 32, 111-115. https://doi.org/10.1016/j.intimp.2015.12.042
Lima-Cabello, E., García-Mediavilla, M. V., Miquilena-Colina, M. E., Vargas-Castrillón, J., Lozano-Rodríguez, T., Fernández-Bermejo, M., Olcoz, J. L., González-Gallego, J., García-Monzón, C., & Sánchez-Campos, S. (2011). Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C. Clinical Science (London, England: 1979), 120(6), 239-250. https://doi.org/10.1042/cs20100387
Liu, M., Yang, W., Liu, S., Hock, D., Zhang, B., Huo, R. Y., Tong, X., & Yan, H. (2018). LXRalpha is expressed at higher levels in healthy people compared to atherosclerosis patients and its over-expression polarizes macrophages towards an anti-inflammatory MPhi2 phenotype, Clinical and Experimental Hypertension (New York, NY: 1993) 40(3), pp. 213-217. https://doi.org/10.1080/10641963.2017.1288740
Loren, J., Huang, Z., Laffitte, B. A., & Molteni, V. (2013). Liver X receptor modulators: A review of recently patented compounds (2009 - 2012). Expert Opinion on Therapeutic Patents, 23(10), 1317-1335. https://doi.org/10.1517/13543776.2013.814640
Ma, K. L., Ruan, X. Z., Powis, S. H., Chen, Y., Moorhead, J. F., & Varghese, Z. (2008). Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology (Baltimore, Md), 48(3), 770-781. https://doi.org/10.1002/hep.22423
Ma, Z., Deng, C., Hu, W., Zhou, J., Fan, C., Di, S., Liu, D., Yang, Y., & Wang, D. (2017). Liver X receptors and their agonists: Targeting for cholesterol homeostasis and cardiovascular diseases. Current Issues in Molecular Biology, 22, 41-64. https://doi.org/10.21775/cimb.022.041
Maqdasy, S., Trousson, A., Tauveron, I., Volle, D. H., Baron, S., & Lobaccaro, J. M. (2016). Once and for all, LXRalpha and LXRbeta are gatekeepers of the endocrine system. Molecular Aspects of Medicine, 49, 31-46. https://doi.org/10.1016/j.mam.2016.04.001
Ménégaut, L., Thomas, C., Jalil, A., Julla, J. B., Magnani, C., Ceroi, A., Basmaciyan, L., Dumont, A., Le Goff, W., Mathew, M. J., Rébé, C., Dérangère, V., Laubriet, A., Crespy, V., Pais de Barros, J. P., Steinmetz, E., Venteclef, N., Saas, P., Lagrost, L., & Masson, D. (2020). Interplay between liver X receptor and hypoxia inducible factor 1α potentiates interleukin-1β production in human macrophages. Cell Reports, 31(7), 107665. https://doi.org/10.1016/j.celrep.2020.107665
Morales, J. R., Ballesteros, I., Deniz, J. M., Hurtado, O., Vivancos, J., Nombela, F., Lizasoain, I., Castrillo, A., & Moro, M. A. (2008). Activation of liver X receptors promotes neuroprotection and reduces brain inflammation in experimental stroke. Circulation, 118(14), 1450-1459. https://doi.org/10.1161/circulationaha.108.782300
Noelia, A. G., & Castrillo, A. (2011). Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochimica et Biophysica Acta, 1812(8), 982-994. https://doi.org/10.1016/j.bbadis.2010.12.015
Na, T. Y., Han, Y. H., Ka, N. L., Park, H. S., Kang, Y. P., Kwon, S. W., Lee, B. H., & Lee, M. O. (2015). 22-S-Hydroxycholesterol protects against ethanol-induced liver injury by blocking the auto/paracrine activation of MCP-1 mediated by LXRα. The Journal of Pathology, 235(5), 710-720. https://doi.org/10.1002/path.4494
Natunen, T., Martiskainen, H., Sarajarvi, T., Helisalmi, S., Pursiheimo, J. P., Viswanathan, J., Laitinen, M., Makinen, P., Kauppinen, T., Rauramaa, T., Leinonen, V., Alafuzoff, I., Haapasalo, A., Soininen, H., & Hiltunen, M. (2013). Effects of NR1H3 genetic variation on the expression of liver X receptor alpha and the progression of Alzheimer's disease. PLOS One, 8(11), e80700. https://doi.org/10.1371/journal.pone.0080700
Nunomura, S., Okayama, Y., Matsumoto, K., Hashimoto, N., Endo-Umeda, K., Terui, T., Makishima, M., & Ra, C. (2015). Activation of LXRs using the synthetic agonist GW3965 represses the production of pro-inflammatory cytokines by murine mast cells. Allergology International, 64, S11-S17. https://doi.org/10.1016/j.alit.2015.03.001
Ozasa, H., Ayaori, M., Iizuka, M., Terao, Y., Uto-Kondo, H., Yakushiji, E., Takiguchi, S., Nakaya, K., Hisada, T., Uehara, Y., Ogura, M., Sasaki, M., Komatsu, T., Horii, S., Mochizuki, S., Yoshimura, M., & Ikewaki, K. (2011). Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARγ/LXRα pathway: Findings from in vitro and ex vivo studies. Atherosclerosis, 219(1), 141-150. https://doi.org/10.1016/j.atherosclerosis.2011.07.113
Park, Y., Pham, T. X., & Lee, J. (2012). Lipopolysaccharide represses the expression of ATP-binding cassette transporter G1 and scavenger receptor class B, type I in murine macrophages. Inflammation Research, 61(5), 465-472. https://doi.org/10.1007/s00011-011-0433-3
Peet, D. J., Janowski, B. A., & Mangelsdorf, D. J. (1998). The LXRs: A new class of oxysterol receptors. Current Opinion in Genetics & Development, 8(5), 571-575. https://doi.org/10.1016/s0959-437x(98)80013-0
Quack, M., Frank, C., & Carlberg, C. (2002). Differential nuclear receptor signalling from DR4-type response elements. Journal of Cellular Biochemistry, 86(3), 601-612. https://doi.org/10.1002/jcb.10247
Rangaraju, S., Dammer, E. B., Raza, S. A., Rathakrishnan, P., Xiao, H., Gao, T., Duong, D. M., Pennington, M. W., Lah, J. J., Seyfried, N. T., & Levey, A. I. (2018). Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer's disease. Molecular Neurodegeneration, 13(1), 24. https://doi.org/10.1186/s13024-018-0254-8
Repa, J. J., Li, H., Frank-Cannon, T. C., Valasek, M. A., Turley, S. D., Tansey, M. G., & Dietschy, J. M. (2007). Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. The Journal of Neuroscience, 27(52), 14470-14480. https://doi.org/10.1523/jneurosci.4823-07.2007
Saenz, J., Alba, G., Reyes-Quiroz, M. E., Geniz, I., Jimenez, J., Sobrino, F., & Santa-Maria, C. (2018). Curcumin enhances LXRalpha in an AMP-activated protein kinase-dependent manner in human macrophages. The Journal of Nutritional Biochemistry, 54, 48-56. https://doi.org/10.1016/j.jnutbio.2017.11.006
Schultz, J. R., Tu, H., Luk, A., Repa, J. J., Medina, J. C., Li, L., Schwendner, S., Wang, S., Thoolen, M., Mangelsdorf, D. J., Lustig, K. D., & Shan, B. (2000). Role of LXRs in control of lipogenesis. Genes & Development, 14(22), 2831-2838. https://doi.org/10.1101/gad.850400
Secor McVoy, J. R., Oughli, H. A., & Oh, U. (2015). Liver X receptor-dependent inhibition of microglial nitric oxide synthase 2. Journal of Neuroinflammation, 12, 27. https://doi.org/10.1186/s12974-015-0247-2
Seol, W., Choi, H. S., & Moore, D. D. (1995). Isolation of proteins that interact specifically with the retinoid X receptor: Two novel orphan receptors. Molecular Endocrinology (Baltimore, Md), 9(1), 72-85. https://doi.org/10.1210/mend.9.1.7760852
Shinar, D. M., Endo, N., Rutledge, S. J., Vogel, R., Rodan, G. A., & Schmidt, A. (1994). NER, a new member of the gene family encoding the human steroid hormone nuclear receptor. Gene, 147(2), 273-276. https://doi.org/10.1016/0378-1119(94)90080-9
Shrestha, E., Hussein, M. A., Savas, J. N., Ouimet, M., Barrett, T. J., Leone, S., Yates, J. R., 3rd, Moore, K. J., Fisher, E. A., & Garabedian, M. J. (2016). Poly(ADP-ribose) polymerase 1 represses Liver X receptor-mediated ABCA1 expression and cholesterol efflux in macrophages. The Journal of Biological Chemistry, 291(21), 11172-11184. https://doi.org/10.1074/jbc.M116.726729
Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J. D., Coopersmith, C. M., Hotchkiss, R. S., Levy, M. M., Marshall, J. C., Martin, G. S., Opal, S. M., Rubenfeld, G. D., van der Poll, T., Vincent, J. L., & Angus, D. C. (2016). The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). Journal of the American Medical Association, 315(8), 801-810. https://doi.org/10.1001/jama.2016.0287.
Smet, M., Van Hoecke, L., De Beuckelaer, A., Vander Beken, S., Naessens, T., Vergote, K., Willart, M., Lambrecht, B. N., Gustafsson, J. A., Steffensen, K. R., & Grooten, J. (2016). Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice. Immunity, Inflammation and Disease, 4(3), 350-361. https://doi.org/10.1002/iid3.118
Song, C., Kokontis, J. M., Hiipakka, R. A., & Liao, S. (1994). Ubiquitous receptor: A receptor that modulates gene activation by retinoic acid and thyroid hormone receptors. Proceedings of the National Academy of Sciences of the United States of America, 91(23), 10809-10813. https://doi.org/10.1073/pnas.91.23.10809
Sorrentino, R., Morello, S., Chen, S., Bonavita, E., & Pinto, A. (2010). The activation of liver X receptors inhibits toll-like receptor-9-induced foam cell formation. Journal of Cellular Physiology, 223(1), 158-167. https://doi.org/10.1002/jcp.22022
Souto, F. O., Castanheira, F. V. S., Trevelin, S. C., Lima, B. H. F., Cebinelli, G. C. M., Turato, W. M., Auxiliadora-Martins, M., Basile-Filho, A., Alves-Filho, J. C., & Cunha, F. Q. (2020). Liver X receptor activation impairs neutrophil functions and aggravates sepsis. The Journal of Infectious Diseases, 221(9), 1542-1553. https://doi.org/10.1093/infdis/jiz635
Spillmann, F., Linthout, Van, Miteva, S., Lorenz, K., Stangl, M., Schultheiss, V., H. P., & Tschope, C. (2014). LXR agonism improves TNF-alpha-induced endothelial dysfunction in the absence of its cholesterol-modulating effects. Atherosclerosis, 232(1), 1-9. https://doi.org/10.1016/j.atherosclerosis.2013.10.001
Su, K., Zhang, G., Zhang, X., & Jiang, W. (2019). Chikusetsusaponin V attenuates lipopolysaccharide-induced acute lung injury in mice by modulation of the NF-kappaB and LXRalpha. International Immunopharmacology, 70, 174-179. https://doi.org/10.1016/j.intimp.2019.02.023
Tang, J., Luo, K., Li, Y., Chen, Q., Tang, D., Wang, D., & Xiao, J. (2015). Capsaicin attenuates LPS-induced inflammatory cytokine production by upregulation of LXRalpha. International Immunopharmacology, 28(1), 264-269. https://doi.org/10.1016/j.intimp.2015.06.007
Tanné, B., Bernier, S., & Dumais, N. (2015). CCR7 receptor expression in mono-MAC-1 cells: Modulation by liver X receptor α activation and prostaglandin E 2. International Journal of Inflammation, 2015, 201571. https://doi.org/10.1155/2015/201571
Taylor, G. A., Carballo, E., Lee, D. M., Lai, W. S., Thompson, M. J., Patel, D. D., Schenkman, D. I., Gilkeson, G. S., Broxmeyer, H. E., Haynes, B. F., & Blackshear, P. J. (1996). A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity, 4(5), 445-454. https://doi.org/10.1016/s1074-7613(00)80411-2
Teboul, M., Enmark, E., Li, Q., Wikström, A. C., Pelto-Huikko, M., & Gustafsson, J. A. (1995). OR-1, a member of the nuclear receptor superfamily that interacts with the 9-cis-retinoic acid receptor. Proceedings of the National Academy of Sciences of the United States of America, 92(6), 2096-2100. https://doi.org/10.1073/pnas.92.6.2096
Töröcsik, D., Baráth, M., Benko, S., Széles, L., Dezso, B., Póliska, S., Hegyi, Z., Homolya, L., Szatmári, I., Lányi, A., & Nagy, L. (2010). Activation of liver X receptor sensitizes human dendritic cells to inflammatory stimuli. Journal of Immunology, 184(10), 5456-5465. https://doi.org/10.4049/jimmunol.0902399
Torra, I. P., Ismaili, N., Feig, J. E., Xu, C. F., Cavasotto, C., Pancratov, R., Rogatsky, I., Neubert, T. A., Fisher, E. A., & Garabedian, M. J. (2008). Phosphorylation of liver X receptor alpha selectively regulates target gene expression in macrophages. Molecular and Cellular Biology, 28(8), 2626-2636. https://doi.org/10.1128/mcb.01575-07
van Tiel, C. M., & de Vries, C. J. (2012). NR4All in the vessel wall. The Journal of Steroid Biochemistry and Molecular Biology, 130(3-5), 186-193. https://doi.org/10.1016/j.jsbmb.2011.01.010
Villablanca, E. J., Raccosta, L., Zhou, D., Fontana, R., Maggioni, D., Negro, A., Sanvito, F., Ponzoni, M., Valentinis, B., Bregni, M., Prinetti, A., Steffensen, K. R., Sonnino, S., Gustafsson, J. A., Doglioni, C., Bordignon, C., Traversari, C., & Russo, V. (2010). Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses. Nature Medicine, 16(1), 98-105. https://doi.org/10.1038/nm.2074
Wang, H. X., Zhang, K., Zhao, L., Tang, J. W., Gao, L. Y., & Wei, Z. P. (2015). Association of liver X receptor α (LXRα) gene polymorphism and ischemic stroke. Genetics and Molecular Research, 14(1), 118-122. https://doi.org/10.4238/2015.January.15.14
Wang, K., Xu, T., Ruan, H., Xiao, H., Liu, J., Song, Z., Cao, Q., Bao, L., Liu, D., Wang, C., Cheng, G., Liang, H., Chen, Z., Yang, H., Chen, K., & Zhang, X. (2019). LXRalpha promotes cell metastasis by regulating the NLRP3 inflammasome in renal cell carcinoma. Cell Death & Disease, 10(3), 159. https://doi.org/10.1038/s41419-019-1345-3
Wang, S., Lin, Y., Yuan, X., Li, F., Guo, L., & Wu, B. (2018). REV-ERBα integrates colon clock with experimental colitis through regulation of NF-κB/NLRP3 axis. Nature Communications, 9(1), 4246. https://doi.org/10.1038/s41467-018-06568-5
Wang, Y., Zhang, X., Wei, Z., Wang, J., Zhang, Y., Shi, M., Yang, Z., & Fu, Y. (2017). Platycodin D suppressed LPS-induced inflammatory response by activating LXRalpha in LPS-stimulated primary bovine mammary epithelial cells. European Journal of Pharmacology, 814, 138-143. https://doi.org/10.1016/j.ejphar.2017.07.037
Wang, Y. Y., Dahle, M. K., Steffensen, K. R., Reinholt, F. P., Collins, J. L., Thiemermann, C., Aasen, A. O., Gustafsson, J. A., & Wang, J. E. (2009). Liver X receptor agonist GW3965 dose-dependently regulates lps-mediated liver injury and modulates posttranscriptional TNF-alpha production and p38 mitogen-activated protein kinase activation in liver macrophages. Shock (Augusta, Ga), 32(5), 548-553. https://doi.org/10.1097/SHK.0b013e3181a47f85
Wang, Y. Y., Dahle, M. K., Agren, J., Myhre, A. E., Reinholt, F. P., Foster, S. J., Collins, J. L., Thiemermann, C., Aasen, A. O., & Wang, J. E. (2006). Activation of the liver X receptor protects against hepatic injury in endotoxemia by suppressing Kupffer cell activation. Shock (Augusta, Ga), 25(2), 141-146. https://doi.org/10.1097/01.shk.0000191377.78144.d9
Wang, Y. Y., Ryg, U., Dahle, M. K., Steffensen, K. R., Thiemermann, C., Chaudry, I. H., Reinholt, F. P., Collins, J. L., Nebb, H. I., Aasen, A. O., Gustafsson, J. A., & Wang, J. E. (2011). Liver X receptor protects against liver injury in sepsis caused by rodent cecal ligation and puncture. Surgical Infections, 12(4), 283-289. https://doi.org/10.1089/sur.2010.066
Willy, P. J., Umesono, K., Ong, E. S., Evans, R. M., Heyman, R. A., & Mangelsdorf, D. J. (1995). LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes & Development, 9(9), 1033-1045. https://doi.org/10.1101/gad.9.9.1033
Worthington, M. T., Amann, B. T., Nathans, D., & Berg, J. M. (1996). Metal binding properties and secondary structure of the zinc-binding domain of Nup475. Proceedings of the National Academy of Sciences of the United States of America, 93(24), 13754-13759. https://doi.org/10.1073/pnas.93.24.13754
Wouters, E., de Wit, N. M., Vanmol, J., van der Pol, S. M. A., van Het Hof, B., Sommer, D., Loix, M., Geerts, D., Gustafsson, J. A., Steffensen, K. R., Vanmierlo, T., Bogie, J. F. J., Hendriks, J. J. A., & de Vries, H. E. (2019). Liver X receptor alpha is important in maintaining blood-brain barrier function. Frontiers in Immunology, 10, 1811. https://doi.org/10.3389/fimmu.2019.01811
Wu, C., Hussein, M. A., Shrestha, E., Leone, S., Aiyegbo, M. S., Lambert, W. M., Pourcet, B., Cardozo, T., Gustafson, J. A., Fisher, E. A., Pineda-Torra, I., & Garabedian, M. J. (2015). Modulation of macrophage gene expression via liver X receptor alpha serine 198 phosphorylation. Molecular and Cellular Biology, 35(11), 2024-2034. https://doi.org/10.1128/mcb.00985-14
Wu, J., Zhang, Y., Wang, N., Davis, L., Yang, G., Wang, X., Zhu, Y., Breyer, M. D., & Guan, Y. (2004). Liver X receptor-alpha mediates cholesterol efflux in glomerular mesangial cells. American Journal of Physiology Renal Physiology, 287(5), F886-F895. https://doi.org/10.1152/ajprenal.00123.2004
Wu, S., Yin, R., Ernest, R., Li, Y., Zhelyabovska, O., Luo, J., Yang, Y., & Yang, Q. (2009). Liver X receptors are negative regulators of cardiac hypertrophy via suppressing NF-kappaB signalling. Cardiovascular Research, 84(1), 119-126. https://doi.org/10.1093/cvr/cvp180
Xiao, J., Chen, Q., Tang, D., Ou, W., Wang, J., Mo, Z., Tang, C., Peng, L., & Wang, D. (2017). Activation of liver X receptors promotes inflammatory cytokine mRNA degradation by upregulation of tristetraprolin. Acta Biochimica et Biophysica Sinica, 49(3), 277-283. https://doi.org/10.1093/abbs/gmw136
Yang, Y., He, Y., Wang, X., Liang, Z., He, G., Zhang, P., Zhu, H., Xu, N., & Liang, S. (2017). Protein SUMOylation modification and its associations with disease. Open Biology, 7(10), 170167. https://doi.org/10.1098/rsob.170167
Yu, S. X., Chen, W., Hu, X. Z., Feng, S. Y., Li, K. Y., Qi, S., Lei, Q. Q., Hu, G. Q., Li, N., Zhou, F. H., Ma, C. Y., Du, C. T., & Yang, Y. J. (2017). Liver X receptors agonists suppress NLRP3 inflammasome activation. Cytokine, 91, 30-37. https://doi.org/10.1016/j.cyto.2016.12.003
Zeng, J., Wu, D., Hu, H., Young, J. A. T., Yan, Z., & Gao, L. (2020). Activation of the liver X receptor pathway inhibits HBV replication in primary human hepatocytes. Hepatology (Baltimore, Md), https://doi.org/10.1002/hep.31217
Zeng, Y., Peng, Y., Tang, K., Wang, Y. Q., Zhao, Z. Y., Wei, X. Y., & Xu, X. L. (2018). Dihydromyricetin ameliorates foam cell formation via LXRalpha-ABCA1/ABCG1-dependent cholesterol efflux in macrophages. Biomedicine & Pharmacotherapy = Biomedecine & pharmacotherapie, 101, 543-552. https://doi.org/10.1016/j.biopha.2018.02.124
Zhang, Y., Breevoort, S. R., Angdisen, J., Fu, M., Schmidt, D. R., Holmstrom, S. R., Kliewer, S. A., Mangelsdorf, D. J., & Schulman, I. G. (2012). Liver LXRalpha expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice. The Journal of Clinical Investigation, 122(5), 1688-1699. https://doi.org/10.1172/jci59817
Zhang-Gandhi, C. X., & Drew, P. D. (2007). Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes. Journal of Neuroimmunology, 183(1-2), 50-59. https://doi.org/10.1016/j.jneuroim.2006.11.007
Zhao, C., & Dahlman-Wright, K. (2010). Liver X receptor in cholesterol metabolism. The Journal of Endocrinology, 204(3), 233-240. https://doi.org/10.1677/joe-09-0271