Targeting orphan nuclear receptors for treatment of metabolic diseases and autoimmunity

Chemistry and Biology

Volumn 19, Issue 1, 2012, Pages 51-59

  Burris, Thomas P ^a   Busby, Scott A ^b   Griffin, Patrick R ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b OPKO Health Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 2,4-THIAZOLIDINEDIONE; 7ALPHA HYDROXYCHOLESTEROL; ACETYLDIGOXIN; CELL RECEPTOR; CHOLESTEROL; CHOLESTEROL SULFATE; DIGOXIN; DIHYDRODIGOXIN; DILAUROYL PHOSPHATIDYLCHOLINE; DIUNDECANOYL PHOSPHATIDYLCHOLINE; HORMONE RECEPTOR BLOCKING AGENT; HORMONE RECEPTOR STIMULATING AGENT; LIVER RECEPTOR HOMOLOG 1; MRL 20; MRL 24; N (2,2,2 TRIFLUOROETHYL) N [4 [2,2,2 TRIFLUORO 1 HYDROXY 1 (TRIFLUOROMETHOXY)ETHYL]PHENYL]BENZENESULFONAMIDE; NR5A2 PROTEIN, HUMAN; ORPHAN NUCLEAR RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLCHOLINE; PIOGLITAZONE; RETINOIC ACID RECEPTOR; RETINOIC ACID RECEPTOR LIKE ORPHAN RECEPTOR; ROSIGLITAZONE; SR 1001; SR 1664; STEROL; UNCLASSIFIED DRUG; URSOLIC ACID;

AUTOIMMUNE DISEASE; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CHEMISTRY; DRUG ANTAGONISM; DRUG MECHANISM; DRUG POTENTIATION; HUMAN; IMMUNE RESPONSE; INSULIN RESISTANCE; METABOLIC DISORDER; METABOLISM; MULTIPLE SCLEROSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PROTEIN TARGETING; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; TH17 CELL;

AUTOIMMUNE DISEASES; HUMANS; METABOLIC DISEASES; ORPHAN NUCLEAR RECEPTORS; PHOSPHATIDYLCHOLINES; PPAR GAMMA; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, RETINOIC ACID; STEROLS; THIAZOLIDINEDIONES;

EID: 84856397813     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2011.12.011     Document Type: Review

References (80)

1. J.J. Acton 3rd, R.M. Black, A.B. Jones, D.E. Moller, L. Colwell, T.W. Doebber, K.L. Macnaul, J. Berger, and H.B. Wood Benzoyl 2-methyl indoles as selective PPARgamma modulators Bioorg. Med. Chem. Lett. 15 2005 357 362 (Pubitemid 39647150)
2. E. André, F. Conquet, M. Steinmayr, S.C. Stratton, V. Porciatti, and M. Becker-André Disruption of retinoid-related orphan receptor beta changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice EMBO J. 17 1998 3867 3877 (Pubitemid 28333973)
3. E. André, K. Gawlas, and M. Becker-André A novel isoform of the orphan nuclear receptor RORbeta is specifically expressed in pineal gland and retina Gene 216 1998 277 283 (Pubitemid 28408189)
4. M. Becker-André, E. André, and J.F. DeLamarter Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences Biochem. Biophys. Res. Commun. 194 1993 1371 1379 (Pubitemid 23255034)
5. A.H. Berg, T.P. Combs, X.L. Du, M. Brownlee, and P.E. Scherer The adipocyte-secreted protein Acrp30 enhances hepatic insulin action Nat. Med. 7 2001 947 953 (Pubitemid 32756433)
6. J.P. Berger, T.E. Akiyama, and P.T. Meinke PPARs: therapeutic targets for metabolic disease Trends Pharmacol. Sci. 26 2005 244 251 (Pubitemid 40603072)
7. J.P. Berger, A.E. Petro, K.L. Macnaul, L.J. Kelly, B.B. Zhang, K. Richards, A. Elbrecht, B.A. Johnson, G.C. Zhou, and T.W. Doebber Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator Mol. Endocrinol. 17 2003 662 676 (Pubitemid 36403578)
8. E. Bettelli, T. Korn, M. Oukka, and V.K. Kuchroo Induction and effector functions of T(H)17 cells Nature 453 2008 1051 1057 (Pubitemid 351871737)
9. T.P. Burris Nuclear hormone receptors for heme: REV-ERBalpha and REV-ERBbeta are ligand-regulated components of the mammalian clock Mol. Endocrinol. 22 2008 1509 1520 (Pubitemid 351920387)
10. C. Carlberg, R. Hooft van Huijsduijnen, J.K. Staple, J.F. DeLamarter, and M. Becker-André RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers Mol. Endocrinol. 8 1994 757 770 (Pubitemid 24179668)
11. H.J. Cha, M.T. Park, H.Y. Chung, N.D. Kim, H. Sato, M. Seiki, and K.W. Kim Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT1080 human fibrosarcoma cells Oncogene 16 1998 771 778 (Pubitemid 28076088)
12. J.H. Choi, A.S. Banks, J.L. Estall, S. Kajimura, P. Boström, D. Laznik, J.L. Ruas, M.J. Chalmers, T.M. Kamenecka, and M. Blüher Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5 Nature 466 2010 451 456
13. D.J. Cua, J. Sherlock, Y. Chen, C.A. Murphy, B. Joyce, B. Seymour, L. Lucian, W. To, S. Kwan, and T. Churakova Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain Nature 421 2003 744 748 (Pubitemid 36227625)
14. E.V. Dang, J. Barbi, H.-Y. Yang, D. Jinasena, H. Yu, Y. Zheng, Z. Bordman, J. Fu, Y. Kim, and H.-R. Yen Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1 Cell 146 2011 772 784
15. C. Day Thiazolidinediones: a new class of antidiabetic drugs Diabet. Med. 16 1999 179 192
16. H. Duez, and B. Staels Rev-erb-alpha: an integrator of circadian rhythms and metabolism J. Appl. Physiol. 107 2009 1972 1980
17. I.A. Ferber, S. Brocke, C. Taylor-Edwards, W. Ridgway, C. Dinisco, L. Steinman, D. Dalton, and C.G. Fathman Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) J. Immunol. 156 1996 5 7
18. S. Fujita-Sato, S. Ito, T. Isobe, T. Ohyama, K. Wakabayashi, K. Morishita, O. Ando, and F. Isono Structural basis of digoxin that antagonizes RORgamma t receptor activity and suppresses Th17 cell differentiation and interleukin (IL)-17 production J. Biol. Chem. 286 2011 31409 31417
19. V. Gigure, M. Tini, G. Flock, E. Ong, R.M. Evans, and G. Otulakowski Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors Genes Dev. 8 1994 538 553
20. B.A. Hamilton, W.N. Frankel, A.W. Kerrebrock, T.L. Hawkins, W. FitzHugh, K. Kusumi, L.B. Russell, K.L. Mueller, V. van Berkel, and B.W. Birren Disruption of the nuclear hormone receptor RORalpha in staggerer mice Nature 379 1996 736 739 (Pubitemid 26061737)
21. L.E. Harrington, R.D. Hatton, P.R. Mangan, H. Turner, T.L. Murphy, K.M. Murphy, and C.T. Weaver Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages Nat. Immunol. 6 2005 1123 1132 (Pubitemid 41541790)
22. T. Hirose, R.J. Smith, and A.M. Jetten ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle Biochem. Biophys. Res. Commun. 205 1994 1976 1983
23. G.S. Hotamisligil, N.S. Shargill, and B.M. Spiegelman Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance Science 259 1993 87 91 (Pubitemid 23036092)
24. E.D. Hu, J.B. Kim, P. Sarraf, and B.M. Spiegelman Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma Science 274 1996 2100 2103 (Pubitemid 27020707)
25. J.R. Huh, M.W.L. Leung, P.X. Huang, D.A. Ryan, M.R. Krout, R.R.V. Malapaka, J. Chow, N. Manel, M. Ciofani, and S.V. Kim Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity Nature 472 2011 486 490
26. I.I. Ivanov, B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, D.J. Cua, and D.R. Littman The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells Cell 126 2006 1121 1133 (Pubitemid 44380299)
27. M.A. Jimenez, P. Akerblad, M. Sigvardsson, and E.D. Rosen Critical role for Ebf1 and Ebf2 in the adipogenic transcriptional cascade Mol. Cell. Biol. 27 2007 743 757 (Pubitemid 46080139)
28. L.H. Jin, D. Martynowski, S.Y. Zheng, T. Wada, W. Xie, and Y. Li Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma Mol. Endocrinol. 24 2010 923 929
29. J. Kallen, J.M. Schlaeppi, F. Bitsch, I. Delhon, and B. Fournier Crystal structure of the human RORalpha Ligand binding domain in complex with cholesterol sulfate at 2.2 A J. Biol. Chem. 279 2004 14033 14038 (Pubitemid 38468938)
30. J.A. Kallen, J.M. Schlaeppi, F. Bitsch, S. Geisse, M. Geiser, I. Delhon, and B. Fournier X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha Structure 10 2002 1697 1707 (Pubitemid 35452576)
31. H.S. Kang, M. Angers, J.Y. Beak, X. Wu, J.M. Gimble, T. Wada, W. Xie, J.B. Collins, S.F. Grissom, and A.M. Jetten Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism Physiol. Genom. 31 2007 281 294 (Pubitemid 350014406)
32. E. Kassi, T.G. Sourlingas, M. Spiliotaki, Z. Papoutsi, H. Pratsinis, N. Aligiannis, and P. Moutsatsou Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells Cancer Invest. 27 2009 723 733
33. E.E. Kershaw, and J.S. Flier Adipose tissue as an endocrine organ J. Clin. Endocrinol. Metab. 89 2004 2548 2556 (Pubitemid 38766330)
34. S.A. Kliewer, J.M. Lehmann, and T.M. Willson Orphan nuclear receptors: shifting endocrinology into reverse Science 284 1999 757 760 (Pubitemid 29291332)
35. I.N. Krylova, E.P. Sablin, J. Moore, R.X. Xu, G.M. Waitt, J.A. MacKay, D. Juzumiene, J.M. Bynum, K. Madauss, and V. Montana Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1 Cell 120 2005 343 355 (Pubitemid 40222429)
36. N. Kumar, L.A. Solt, J.J. Conkright, Y. Wang, M.A. Istrate, S.A. Busby, R. Garcia-Ordonez, T.P. Burris, and P.R. Griffin The benzenesulfoamide T0901317 [N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl) ethyl]phenyl]-benzenesulfonamide] is a novel retinoic acid receptor-related orphan receptor-alpha/gamma inverse agonist Mol. Pharmacol. 77 2010 228 236
37. N. Kumar, D.J. Kojetin, L.A. Solt, K.G. Kumar, P. Nuhant, D.R. Duckett, M.D. Cameron, A.A. Butler, W.R. Roush, and P.R. Griffin Identification of SR3335 (ML-176): a synthetic ror alpha selective inverse agonist ACS Chem. Biol. 6 2011 218 222
38. C. Lagathu, L. Yvan-Charvet, J.P. Bastard, M. Maachi, A. Quignard-Boulangé, J. Capeau, and M. Caron Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes Diabetologia 49 2006 2162 2173 (Pubitemid 44168485)
39. P. Lau, R.L. Fitzsimmons, S. Raichur, S.C.M. Wang, A. Lechtken, and G.E.O. Muscat The orphan nuclear receptor, ROR alpha, regulates gene expression that controls lipid metabolism - Staggerer (sg/sg) mice are resistant to diet-induced obesity J. Biol. Chem. 283 2008 18411 18421
40. J.M. Lee, Y.K. Lee, J.L. Mamrosh, S.A. Busby, P.R. Griffin, M.C. Pathak, E.A. Ortlund, and D.D. Moore A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects Nature 474 2011 506 510
41. Y.K. Lee, and D.D. Moore Liver receptor homolog-1, an emerging metabolic modulator Front. Biosci. 13 2008 5950 5958
42. Y.-K. Lee, D.R. Schmidt, C.L. Cummins, M. Choi, L. Peng, Y. Zhang, B. Goodwin, R.E. Hammer, D.J. Mangelsdorf, and S.A. Kliewer Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis Mol. Endocrinol. 22 2008 1345 1356 (Pubitemid 351786995)
43. J.M. Lehmann, L.B. Moore, T.A. Smith-Oliver, W.O. Wilkison, T.M. Willson, and S.A. Kliewer An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma) J. Biol. Chem. 270 1995 12953 12956
44. Y. Li, M. Choi, G. Cavey, J. Daugherty, K. Suino, A. Kovach, N.C. Bingham, S.A. Kliewer, and H.E. Xu Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1 Mol. Cell 17 2005 491 502 (Pubitemid 40269114)
45. L.L. Lipscombe, T. Gomes, L.E. Lévesque, J.E. Hux, D.N. Juurlink, and D.A. Alter Thiazolidinediones and cardiovascular outcomes in older patients with diabetes JAMA 298 2007 2634 2643 (Pubitemid 350254955)
46. D.R. Littman, and A.Y. Rudensky Th17 and regulatory T cells in mediating and restraining inflammation Cell 140 2010 845 858
47. A. Mamontova, S. Seguret-Mace, B. Esposito, C. Chaniale, M. Bouly, N. Delhaye-Bouchaud, G. Luc, B. Staels, N. Duverger, and J. Mariani Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor ROR alpha Circulation 98 1998 2738 2743 (Pubitemid 28564010)
48. D.J. Mangelsdorf, and R.M. Evans The RXR heterodimers and orphan receptors Cell 83 1995 841 850 (Pubitemid 26006526)
49. D.J. Mangelsdorf, C. Thummel, M. Beato, P. Herrlich, G. Schütz, K. Umesono, B. Blumberg, P. Kastner, M. Mark, P. Chambon, and R.M. Evans The nuclear receptor superfamily: the second decade Cell 83 1995 835 839
50. M.I. Masana, I.C. Sumaya, M. Becker-Andre, and M.L. Dubocovich Behavioral characterization and modulation of circadian rhythms by light and melatonin in C3H/HeN mice homozygous for the ROR beta knockout Am. J. Physiol. Regul. Integr. Comp. Physiol. 292 2007 R2357 R2367
51. A. Medvedev, Z.H. Yan, T. Hirose, V. Gigure, and A.M. Jetten Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and characterization of its response element Gene 181 1996 199 206 (Pubitemid 26418270)
52. S.A. Miller, and A.S. Weinmann Common themes emerge in the transcriptional control of T helper and developmental cell fate decisions regulated by the T-box, GATA and ROR families Immunology 126 2009 306 315
53. R.F. Morrison, and S.R. Farmer Hormonal signaling and transcriptional control of adipocyte differentiation J. Nutr. 130 2000 3116S 3121S (Pubitemid 32005352)
54. C.A. Murphy, C.L. Langrish, Y. Chen, W. Blumenschein, T. McClanahan, R.A. Kastelein, J.D. Sedgwick, and D.J. Cua Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation J. Exp. Med. 198 2003 1951 1957 (Pubitemid 38032126)
55. E.A. Ortlund, Y. Lee, I.H. Solomon, J.M. Hager, R. Safi, Y. Choi, Z.Q. Guan, A. Tripathy, C.R.H. Raetz, and D.P. McDonnell Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP Nat. Struct. Mol. Biol. 12 2005 357 363 (Pubitemid 43093091)
56. H. Park, Z.X. Li, X.O. Yang, S.H. Chang, R. Nurieva, Y.H. Wang, Y. Wang, L. Hood, Z. Zhu, Q. Tian, and C. Dong A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 Nat. Immunol. 6 2005 1133 1141 (Pubitemid 41541791)
57. S. Raghuram, K.R. Stayrook, P. Huang, P.M. Rogers, A.K. Nosie, D.B. McClure, L.L. Burris, S. Khorasanizadeh, T.P. Burris, and F. Rastinejad Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta Nat. Struct. Mol. Biol. 14 2007 1207 1213 (Pubitemid 350223341)
58. M.J. Reginato, and M.A. Lazar Mechanisms by which thiazolidinediones enhance insulin action Trends Endocrinol. Metab. 10 1999 9 13 (Pubitemid 29288704)
59. R.J. Santen, H. Brodie, E.R. Simpson, P.K. Siiteri, and A. Brodie History of aromatase: saga of an important biological mediator and therapeutic target Endocr. Rev. 30 2009 343 375
60. A.V. Schwartz, D.E. Sellmeyer, E. Vittinghoff, L. Palermo, B. Lecka-Czernik, K.R. Feingold, E.S. Strotmeyer, H.E. Resnick, L. Carbone, and B.A. Beamer Thiazolidinedione use and bone loss in older diabetic adults J. Clin. Endocrinol. Metab. 91 2006 3349 3354 (Pubitemid 44402103)
61. A.M. Sharma, and B. Staels Review: Peroxisome proliferator-activated receptor gamma and adipose tissue - understanding obesity-related changes in regulation of lipid and glucose metabolism J. Clin. Endocrinol. Metab. 92 2007 386 395
62. L.A. Solt, D.J. Kojetin, and T.P. Burris The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis Future Med. Chem. 3 2011 623 638
63. L.A. Solt, N. Kumar, P. Nuhant, Y.J. Wang, J.L. Lauer, J. Liu, M.A. Istrate, T.M. Kamenecka, W.R. Roush, and D. Vidović Suppression of T(H)17 differentiation and autoimmunity by a synthetic ROR ligand Nature 472 2011 491 494
64. M. Steinmayr, E. André, F. Conquet, L. Rondi-Reig, N. Delhaye-Bouchaud, N. Auclair, H. Daniel, F. Crépel, J. Mariani, C. Sotelo, and M. Becker-André staggerer phenotype in retinoid-related orphan receptor alpha-deficient mice Proc. Natl. Acad. Sci. USA 95 1998 3960 3965 (Pubitemid 28173236)
65. C.M. Steppan, S.T. Bailey, S. Bhat, E.J. Brown, R.R. Banerjee, C.M. Wright, H.R. Patel, R.S. Ahima, and M.A. Lazar The hormone resistin links obesity to diabetes Nature 409 2001 307 312 (Pubitemid 32151228)
66. P. Tontonoz, E.D. Hu, and B.M. Spiegelman Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor Cell 79 1994 1147 1156
67. M.E. Trujillo, and P.E. Scherer Adipose tissue-derived factors: impact on health and disease Endocr. Rev. 27 2006 762 778 (Pubitemid 44936059)
68. Y. Wang, N. Kumar, C. Crumbley, P.R. Griffin, and T.P. Burris A second class of nuclear receptors for oxysterols: Regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol) Biochim. Biophys. Acta 1801 2010 917 923
69. Y. Wang, N. Kumar, L.A. Solt, T.I. Richardson, L.M. Helvering, C. Crumbley, R.A. Garcia-Ordonez, K.R. Stayrook, X. Zhang, and S. Novick Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands J. Biol. Chem. 285 2010 5013 5025
70. W. Wei, X.D. Wang, M. Yang, L.C. Smith, P.C. Dechow, J. Sonoda, R.M. Evans, and Y. Wan PGC1beta mediates PPARgamma activation of osteoclastogenesis and rosiglitazone-induced bone loss Cell Metab. 11 2010 503 516
71. D.O. Willenborg, S. Fordham, C.C.A. Bernard, W.B. Cowden, and I.A. Ramshaw IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis J. Immunol. 157 1996 3223 3227 (Pubitemid 126449130)
72. T.M. Willson, J.E. Cobb, D.J. Cowan, R.W. Wiethe, I.D. Correa, S.R. Prakash, K.D. Beck, L.B. Moore, S.A. Kliewer, and J.M. Lehmann The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones J. Med. Chem. 39 1996 665 668
73. T.M. Willson, M.H. Lambert, and S.A. Kliewer Peroxisome proliferator-activated receptor gamma and metabolic disease Annu. Rev. Biochem. 70 2001 341 367 (Pubitemid 32662214)
74. Z.D. Wu, N.L.R. Bucher, and S.R. Farmer Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids Mol. Cell. Biol. 16 1996 4128 4136 (Pubitemid 26251212)
75. T. Xu, X. Wang, B. Zhong, R.I. Nurieva, S. Ding, and C. Dong Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein J. Biol. Chem. 286 2011 22707 22710
76. T. Yamauchi, Y. Nio, T. Maki, M. Kobayashi, T. Takazawa, M. Iwabu, M. Okada-Iwabu, S. Kawamoto, N. Kubota, and T. Kubota Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions Nat. Med. 13 2006 332 339 (Pubitemid 46376688)
77. X.O. Yang, B.P. Pappu, R. Nurieva, A. Akimzhanov, H.S. Kang, Y. Chung, L. Ma, B. Shah, A.D. Panopoulos, and K.S. Schluns T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma Immunity 28 2008 29 39
78. L. Yin, N. Wu, J.C. Curtin, M. Qatanani, N.R. Szwergold, R.A. Reid, G.M. Waitt, D.J. Parks, K.H. Pearce, G.B. Wisely, and M.A. Lazar Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways Science 318 2007 1786 1789 (Pubitemid 350274391)
79. L. Yin, N. Wu, and M.A. Lazar Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism Nucl. Recept. Signal. 8 2010 e001
80. G.X. Zhang, B. Gran, S. Yu, J.F. Li, I. Siglienti, X.H. Chen, M. Kamoun, and A. Rostami Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system J. Immunol. 170 2003 2153 2160 (Pubitemid 36197439)