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BioMol Concepts, Vol. 1 (2010), pp. 381–387 • Copyright by Walter de Gruyter • Berlin • New York. DOI 10.1515/BMC.2010.030 2010/033 Article in press - uncorrected proof Review Liver X receptors and immune regulation Satoshi Nunomura1, Makoto Makishima2 and Chisei Ra1,* 1 Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchikami- cho Itabashi-ku, Tokyo 173-8610, Japan 2 Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of

Introduction Liver X receptors (LXR)α (NR1H3) and β (NR1H2) are two members of the nuclear receptor (NR) family involved in multiple metabolic pathways including energy expenditure (1–3), insulin signaling (4–6), and metabolism of glucose, lipid (7–17), and cholesterol (18–27). They play key roles in atherosclerosis (28, 29), inflammation (7, 30), and CNS development (31, 32). Their main function is to translate physiological (hormonal, metabolic, exercise, or dietary) signals into modification of gene expression. Following ligand binding, they repress or

.J., Devi T.R., Falck J.R., Mangelsdorf D.J., An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha, Nature, 1996, 383, 728–731 http://dx.doi.org/10.1038/383728a0 [13] Apfel R., Benbrook D., Lernhardt E., Ortiz M.A., Salbert G., Pfahl M., A novel orphan receptor-specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone-receptor subfamily, Mol. Cell. Biol., 1994, 14, 7025–7035 [14] Hu Y-W., Zheng L., Wang Q., Regulation of cholesterol homeostasis by liver X receptors, Clin. Chim. Acta, 2010, 411

Horm Mol Biol Clin Invest 2011;8(2):471–478 © 2011 by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HMBCI.2011.125 Liver X receptor agonist downregulates growth hormone signaling in the liver Fahad Zadjali 1 – 3, *, Ruyman Santana-Farre 4 , Mercedes Mirecki-Garrido 4 , Ewa Ellis 5 , Gunnar Norstedt 2 , Leandro Fernandez-Perez 4 and Amilcar Flores-Morales 1 1 Novo Nordisk Foundation Center for Protein Research , Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark 2 Department of Molecular Medicine and Surgery

References 1. Hashimoto K, Matsumoto S, Yamada M, Satoh T, Mori M. Liver X Receptor-α gene expression is positively regulated by thyroid hormone. Endocrinology. 2007; 148:4667-75. 2. Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signalling. J Clin Invest. 2006; 116:607-14. 10.1172/JCI27883 3. Jamroz-Wioeniewska A, Wójcicka G, Horoszewicz K, Be³towski J. Liver X receptors (LXRs). Part II: Nonlipid effects, role in pathology, and therapeutic implications. Postepy Hig Med Dosw. 2007; 61:760-85. 4. Gerbod-Giannone M, Li Y

, Gustafsson JA, Nebb HI. Expression of the insulin-responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptor alpha. J Biol Chem 2003;278:48283–91. 10.1074/jbc.M302287200 40. Griesel BA, Weems J, Russell RA, Abel ED, Humphries KM, Olson AL. Acute inhibition of fatty acid import inhibits LGUT4 transcription in adipose tissue, but not skeletal or cardiac muscle tissue, partly through liver X receptor (LXR) signaling. Diabetes 2010;59:1404–14. 10.2337/db09-1542 41. Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC

detected in neurons and oligodendrocytes in adult brain and in epithelial tissues in 28-week-old fetal brain. Sulfonation of cholesterol, oxysterols, and neurosteroids in the brain is apparently catalyzed by SULT2B1b since expression of nei- ther SULT2A1 nor SULT1E1 was detected in human brain sections. SULT2B1b mRNA and protein were also detected in human U373-MG glioblastoma cells. Both mRNA and protein expression of liver X receptor (LXR)- β , but not LXR- α , were detected in U373-MG cells, and LXR- β acti- vation resulted in a decrease in SULT2B1b protein

.548±0.168 0.705±0.103 0.573±0.067 Triglyceride/protein 0.064 0.108 0.082 0.071 0.155 0.060 0.096 0.238 0.089 0.089 0.158 0.086 Mean±SD 0.080±0.015 0.165±0.054 0.079±0.013 CEC of HDL subfractions No differences in CEC among whole HDL, apoE-containing HDL and apoE-deficient HDL were observed in the absence of the liver X receptor (LXR) agonist ( Figure 2 ). In the presence of the LXR agonist, the CEC of apoE-containing HDL was obviously and significantly increased (1.48±0.18-fold, p <0.01); however, those of whole HDL and apoE-deficient HDL were unchanged and slightly

kits for the determination of triglyceride (TG), cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin-6 (IL-6) were provided by the Nanjing Jiancheng Bioengineering Institute (Nanjing, China). Antibodies against sterol regulatory element binding protein-1c (SREBP-1c) and liver X receptor (LXR-a) were the products of SantaCruz Biotechnology (Shanghai, China). β-Actin antibody and RIPA lysis buffer were from Beyotime Institute of Biotechnology (Shanghai, China). The 2×Taq PCR Master Mix was purchased from Real

], [ 9 ], [ 10 ], [ 11 ]. Recent studies highlighted the role of Liver X receptors (LXR) in cancer, and LXR activation seems to be protective in cancer prevention [ 12 ], [ 13 ]. Consequently, in cancer therapy, LXR has become a target recently. LXR is a member of nuclear receptor superfamily. Two LXRs, LXRα and LXRβ, have been expressed in different tissues. While LXRα is expressed highly in liver, intestine, kidney, spleen, macrophages and adipose tissue, LXRβ is expressed more ubiquitously [ 14 ]. Nuclear receptors are responsible for the regulation of gene