Journal of Hepatology
Volume 51, Issue 5 , Pages 898-908 , November 2009

Redundant roles for cJun-N-terminal kinase 1 and 2 in interleukin-1β-mediated reduction and modification of murine hepatic nuclear retinoid X receptor α

Received 22 December 2008 ,Revised 29 May 2009 ,Accepted 23 June 2009.

References 

  1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–454
  2. Geier A, Fickert P, Trauner M. Mechanisms of disease: mechanisms and clinical implications of cholestasis in sepsis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:574–585
  3. Schwabe RF, Seki E, Brenner DA. Toll-like receptor signaling in the liver. Gastroenterology. 2006;130:1886–1900
  4. Migita K, Abiru S, Nakamura M, Komori A, Yoshida Y, Yokoyama T, et al. Lipopolysaccharide signaling induces serum amyloid A (SAA) synthesis in human hepatocytes in vitro. FEBS Lett. 2004;569:235–239
  5. Liu S, Gallo DJ, Green AM, Williams DL, Gong X, Shapiro RA, et al. Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide. Infect Immun. 2002;70:3433–3442
  6. Ghose R, Zimmerman TL, Thevananther S, Karpen SJ. Endotoxin leads to rapid subcellular re-localization of hepatic RXRalpha: a novel mechanism for reduced hepatic gene expression in inflammation. Nucl Recept. 2004;2:4
  7. Trauner M, Arrese M, Lee H, Boyer JL, Karpen SJ. Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors. J Clin Invest. 1998;101:2092–2100
  8. Li D, Zimmerman TL, Thevananther S, Lee HY, Kurie JM, Karpen SJ. Interleukin-1 beta-mediated suppression of RXR:RAR transactivation of the Ntcp promoter is JNK-dependent. J Biol Chem. 2002;277:31416–31422
  9. Ghose R, Mulder J, von Furstenberg RJ, Thevananther S, Kuipers F, Karpen SJ. Rosiglitazone attenuates suppression of RXRalpha-dependent gene expression in inflamed liver. J Hepatol. 2007;46:115–123
  10. Beigneux AP, Moser AH, Shigenaga JK, Grunfeld C, Feingold KR. The acute phase response is associated with retinoid X receptor repression in rodent liver. J Biol Chem. 2000;275:16390–16399
  11. Geier A, Dietrich CG, Voigt S, Ananthanarayanan M, Lammert F, Schmitz A, et al. Cytokine-dependent regulation of hepatic organic anion transporter gene transactivators in mouse liver. Am J Physiol Gastrointest Liver Physiol. 2005;289:G831–G841
  12. Kim MS, Shigenaga J, Moser A, Feingold K, Grunfeld C. Repression of farnesoid X receptor during the acute phase response. J Biol Chem. 2003;278:8988–8995
  13. Lickteig AJ, Slitt AL, Arkan MC, Karin M, Cherrington NJ. Differential regulation of hepatic transporters in the absence of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and nuclear factor-kappaB in two models of cholestasis. Drug Metab Dispos. 2007;35:402–409
  14. Teng S, Piquette-Miller M. The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J Pharmacol Exp Ther. 2005;312:841–848
  15. Zimmerman TL, Thevananther S, Ghose R, Burns AR, Karpen SJ. Nuclear export of retinoid X receptor alpha in response to interleukin-1beta-mediated cell signaling: roles for JNK and SER260. J Biol Chem. 2006;281:15434–15440
  16. Geier A, Wagner M, Dietrich CG, Trauner M. Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration. Biochim Biophys Acta. 2007;1773:283–308
  17. Kosters A, Karpen SJ. Bile acid transporters in health and disease. Xenobiotica. 2008;38:1043–1071
  18. Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNFalpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol. 2006;290:G583–G589
  19. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103:239–252
  20. Dong C, Yang DD, Wysk M, Whitmarsh AJ, Davis RJ, Flavell RA. Defective T cell differentiation in the absence of Jnk1. Science. 1998;282:2092–2095
  21. Yang DD, Conze D, Whitmarsh AJ, Barrett T, Davis RJ, Rincon M, et al. Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2. Immunity. 1998;9:575–585
  22. Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner EF. Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev. 1999;89:115–124
  23. Conze D, Krahl T, Kennedy N, Weiss L, Lumsden J, Hess P, et al. C-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation. J Exp Med. 2002;195:811–823
  24. Jaeschke A, Rincon M, Doran B, Reilly J, Neuberg D, Greiner DL, et al. Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes. Proc Natl Acad Sci USA. 2005;102:6931–6935
  25. She QB, Chen N, Bode AM, Flavell RA, Dong Z. Deficiency of c-Jun-NH(2)-terminal kinase-1 in mice enhances skin tumor development by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 2002;62:1343–1348
  26. Qiao L, Han SI, Fang Y, Park JS, Gupta S, Gilfor D, et al. Bile acid regulation of C/EBPbeta, CREB, and c-Jun function, via the extracellular signal-regulated kinase and c-Jun NH2-terminal kinase pathways, modulates the apoptotic response of hepatocytes. Mol Cell Biol. 2003;23:3052–3066
  27. Czaja MJ. Cell signaling in oxidative stress-induced liver injury. Semin Liver Dis. 2007;27:378–389
  28. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420:333–336
  29. Dong C, Yang DD, Tournier C, Whitmarsh AJ, Xu J, Davis RJ, et al. JNK is required for effector T-cell function but not for T-cell activation. Nature. 2000;405:91–94
  30. Arbour N, Naniche D, Homann D, Davis RJ, Flavell RA, Oldstone MB. C-Jun NH(2)-terminal kinase (JNK)1 and JNK2 signaling pathways have divergent roles in CD8(+) T cell-mediated antiviral immunity. J Exp Med. 2002;195:801–810
  31. Sabapathy K, Hu Y, Kallunki T, Schreiber M, David JP, Jochum W, et al. JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. Curr Biol. 1999;9:116–125
  32. Schattenberg JM, Singh R, Wang Y, Lefkowitch JH, Rigoli RM, Scherer PE, et al. JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology. 2006;43:163–172
  33. Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15:74–80
  34. Moshage H. Cytokines and the hepatic acute phase response. J Pathol. 1997;181:257–266
  35. Ruminy P, Gangneux C, Claeyssens S, Scotte M, Daveau M, Salier JP. Gene transcription in hepatocytes during the acute phase of a systemic inflammation: from transcription factors to target genes. Inflamm Res. 2001;50:383–390
  36. Shulman AI, Mangelsdorf DJ. Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med. 2005;353:604–615
  37. Karpen SJ. Nuclear receptor regulation of hepatic function. J Hepatol. 2002;36:832–850
  38. Itoh M, Adachi M, Yasui H, Takekawa M, Tanaka H, Imai K. Nuclear export of glucocorticoid receptor is enhanced by c-Jun N-terminal kinase-mediated phosphorylation. Mol Endocrinol. 2002;16:2382–2392
  39. Berry MN, Friend DS. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969;43:506–520
  40. Denson LA, Sturm E, Echevarria W, Zimmerman TL, Makishima M, Mangelsdorf DJ, et al. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology. 2001;121:140–147
  41. Geier A, Dietrich CG, Voigt S, Kim SK, Gerloff T, Kullak-Ublick GA, et al. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Hepatology. 2003;38:345–354
  42. Luster MI, Germolec DR, Yoshida T, Kayama F, Thompson M. Endotoxin-induced cytokine gene expression and excretion in the liver. Hepatology. 1994;19:480–488
  43. Gronemeyer H, Gustafsson JA, Laudet V. Principles for modulation of the nuclear receptor superfamily. Nat Rev Drug Discov. 2004;3:950–964
  44. Zollner G, Marschall HU, Wagner M, Trauner M. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations. Mol Pharm. 2006;3:231–251
  45. Kim MS, Sweeney TR, Shigenaga JK, Chui LG, Moser A, Grunfeld C, et al. Tumor necrosis factor and interleukin 1 decrease RXRalpha, PPARalpha, PPARgamma, LXRalpha, and the coactivators SRC-1, PGC-1alpha, and PGC-1beta in liver cells. Metabolism. 2007;56:267–279
  46. Green RM, Beier D, Gollan JL. Regulation of hepatocyte bile salt transporters by endotoxin and inflammatory cytokines in rodents. Gastroenterology. 1996;111:193–198
  47. Hartmann G, Cheung AK, Piquette-Miller M. Inflammatory cytokines, but not bile acids, regulate expression of murine hepatic anion transporters in endotoxemia. J Pharmacol Exp Ther. 2002;303:273–281
  48. Hartmann G, Kim H, Piquette-Miller M. Regulation of the hepatic multidrug resistance gene expression by endotoxin and inflammatory cytokines in mice. Int Immunopharmacol. 2001;1:189–199
  49. Solomon C, White JH, Kremer R. Mitogen-activated protein kinase inhibits 1,25-dihydroxyvitamin D3-dependent signal transduction by phosphorylating human retinoid X receptor alpha. J Clin Invest. 1999;103:1729–1735
  50. Macoritto M, Nguyen-Yamamoto L, Huang DC, Samuel S, Yang XF, Wang TT, et al. Phosphorylation of the human retinoid X receptor alpha at serine 260 impairs coactivator(s) recruitment and induces hormone resistance to multiple ligands. J Biol Chem. 2008;283:4943–4956
  51. Adam-Stitah S, Penna L, Chambon P, Rochette-Egly C. Hyperphosphorylation of the retinoid X receptor alpha by activated c-Jun NH2-terminal kinases. J Biol Chem. 1999;274:18932–18941
  52. Lee HY, Suh YA, Robinson MJ, Clifford JL, Hong WK, Woodgett JR, et al. Stress pathway activation induces phosphorylation of retinoid X receptor. J Biol Chem. 2000;275:32193–32199
  53. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA. 2001;98:13681–13686
  54. Bruck N, Bastien J, Bour G, Tarrade A, Plassat JL, Bauer A, et al. Phosphorylation of the retinoid X receptor at the omega loop, modulates the expression of retinoic-acid-target genes with a promoter context specificity. Cell Signal. 2005;17:1229–1239
  55. Srinivas H, Juroske DM, Kalyankrishna S, Cody DD, Price RE, Xu XC, et al. C-Jun N-terminal kinase contributes to aberrant retinoid signaling in lung cancer cells by phosphorylating and inducing proteasomal degradation of retinoic acid receptor alpha. Mol Cell Biol. 2005;25:1054–1069
  56. Liu B, Wu JF, Zhan YY, Chen HZ, Zhang XY, Wu Q. Regulation of the orphan receptor TR3 nuclear functions by c-Jun N terminal kinase phosphorylation. Endocrinology. 2007;148:34–44
  57. Gao M, Labuda T, Xia Y, Gallagher E, Fang D, Liu YC, et al. Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. Science. 2004;306:271–275

 The underlying research reported in the study was funded by the NIH Institutes of Health (Grant No. DK56239). The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00531-5

doi: 10.1016/j.jhep.2009.06.029

Journal of Hepatology
Volume 51, Issue 5 , Pages 898-908 , November 2009