TLR4 signaling and the inhibition of liver hepcidin expression by alcohol

World Journal of Gastroenterology

Volumn 20, Issue 34, 2014, Pages 12161-12170

  Zmijewski, Emily ^a   Lu, Sizhao ^a   Harrison Findik, Duygu Dee ^a  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Alcoholic liver disease; Inflammation; Iron; Nuclear factor B; Small heterodimer partner protein

Indexed keywords

ALCOHOL; COMPLEMENTARY DNA; DNA BINDING PROTEIN; HEPCIDIN; HETERODIMER; STAT3 PROTEIN; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR RELA; HAMP1 PROTEIN, MOUSE; MESSENGER RNA; RELA PROTEIN, MOUSE; STAT3 PROTEIN, MOUSE; TLR4 PROTEIN, MOUSE;

ALCOHOL CONSUMPTION; ANIMAL EXPERIMENT; ARTICLE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; GENE EXPRESSION; INTERNAL MEDICINE; MALE; MOUSE; NONHUMAN; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN SUBUNIT; REAL TIME POLYMERASE CHAIN REACTION; RNA ISOLATION; SIGNAL TRANSDUCTION; TIME; WESTERN BLOTTING; ANIMAL; BINDING SITE; C3H MOUSE; DISEASE MODEL; DOWN REGULATION; GENETIC TRANSCRIPTION; GENETICS; LIVER; LIVER DISEASES, ALCOHOLIC; METABOLISM; MUTANT MOUSE STRAIN; MUTATION; PHOSPHORYLATION;

ANIMALS; BINDING SITES; DISEASE MODELS, ANIMAL; DOWN-REGULATION; ETHANOL; HEPCIDINS; LIVER; LIVER DISEASES, ALCOHOLIC; MALE; MICE, INBRED C3H; MICE, MUTANT STRAINS; MUTATION; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; RNA, MESSENGER; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION FACTOR RELA; TRANSCRIPTION, GENETIC;

EID: 84909609800     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i34.12161     Document Type: Article

References (47)

1. Duane P, Raja KB, Simpson RJ, Peters TJ. Intestinal iron absorption in chronic alcoholics. Alcohol Alcohol 1992; 27: 539-544 [PMID: 1476557]
2. Lin M, Rippe RA, Niemelä O, Brittenham G, Tsukamoto H. Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages. Am J Physiol 1997; 272: G1355-G1364 [PMID: 9227470]
3. Tsukamoto H, Lin M, Ohata M, Giulivi C, French SW, Brittenham G. Iron primes hepatic macrophages for NF-kappaB activation in alcoholic liver injury. Am J Physiol 1999; 277: G1240-G1250 [PMID: 10600822]
4. Tsukamoto H, Horne W, Kamimura S, Niemelä O, Parkkila S, Ylä-Herttuala S, Brittenham GM. Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest 1995; 96: 620-630 [PMID: 7615836]
5. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loréal O. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001; 276: 7811-7819 [PMID: 11113132]
6. Hunter HN, Fulton DB, Ganz T, Vogel HJ. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. J Biol Chem 2002; 277: 37597-37603 [PMID: 12138110]
7. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306: 2090-2093 [PMID: 15514116 DOI: 10.1126/science.1104742]
8. Nicolas G, Viatte L, Bennoun M, Beaumont C, Kahn A, Vaulont S. Hepcidin, a new iron regulatory peptide. Blood Cells Mol Dis 2002; 29: 327-335 [PMID: 12547223]
9. Harrison-Findik DD, Schafer D, Klein E, Timchenko NA, Kulaksiz H, Clemens D, Fein E, Andriopoulos B, Pantopoulos K, Gollan J. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem 2006; 281: 22974-22982 [PMID: 16737972]
10. Harrison-Findik DD. Role of alcohol in the regulation of iron metabolism. World J Gastroenterol 2007; 13: 4925-4930 [PMID: 17854133]
11. Harrison-Findik DD, Klein E, Crist C, Evans J, Timchenko N, Gollan J. Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcohol. Hepatology 2007; 46: 1979-1985 [PMID: 17763462]
12. Bridle K, Cheung TK, Murphy T, Walters M, Anderson G, Crawford DG, Fletcher LM. Hepcidin is down-regulated in alcoholic liver injury: implications for the pathogenesis of alcoholic liver disease. Alcohol Clin Exp Res 2006; 30: 106-112 [PMID: 16433737]
13. Harrison-Findik DD, Lu S, Zmijewski EM, Jones J, Zimmerman MC. Effect of alcohol exposure on hepatic superoxide generation and hepcidin expression. World J Biol Chem 2013; 4: 119-130 [PMID: 24340135 DOI: 10.4331/wjbc.v4.i4.119]
14. Ohtake T, Saito H, Hosoki Y, Inoue M, Miyoshi S, Suzuki Y, Fujimoto Y, Kohgo Y. Hepcidin is down-regulated in alcohol loading. Alcohol Clin Exp Res 2007; 31: S2-S8 [PMID: 17331161]
15. Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 2005; 102: 1906-1910 [PMID: 15684062]
16. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003; 101: 2461-2463 [PMID: 12433676]
17. Fujimoto M, Uemura M, Nakatani Y, Tsujita S, Hoppo K, Tamagawa T, Kitano H, Kikukawa M, Ann T, Ishii Y, Kojima H, Sakurai S, Tanaka R, Namisaki T, Noguchi R, Higashino T, Kikuchi E, Nishimura K, Takaya A, Fukui H. Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: relation to severity of liver disturbance. Alcohol Clin Exp Res 2000; 24: 48S-54S [PMID: 10803780]
18. Enomoto N, Ikejima K, Yamashina S, Hirose M, Shimizu H, Kitamura T, Takei Y, Sato And N, Thurman RG. Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin. Alcohol Clin Exp Res 2001; 25: 51S-54S [PMID: 11410742]
19. Takei Y, Arteel GE, Bergheim I, Lambert JC, McMullen MR, Nagy LE, Enomoto N, Sato N. Roles of Kupffer cells in alcoholic liver disease. Alcohol Clin Exp Res 2005; 29: 1116-1120
20. Mandrekar P, Szabo G. Signalling pathways in alcohol-induced liver inflammation. J Hepatol 2009; 50: 1258-1266 [PMID: 19398236 DOI: 10.1016/j.jhep.2009.03.007]
21. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11: 373-384 [PMID: 20404851 DOI: 10.1038/ni.1863]
22. Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004; 16: 3-9 [PMID: 14751757]
23. Hritz I, Mandrekar P, Velayudham A, Catalano D, Dolganiuc A, Kodys K, Kurt-Jones E, Szabo G. The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88. Hepatology 2008; 48: 1224-1231 [PMID: 18792393 DOI: 10.1002/hep.22470]
24. Uesugi T, Froh M, Arteel GE, Bradford BU, Thurman RG. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology 2001; 34: 101-108 [PMID: 11431739 DOI: 10.1053/jhep.2001.25350]
25. Bode JG, Albrecht U, Häussinger D, Heinrich PC, Schaper F. Hepatic acute phase proteins - regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-κB-dependent signaling. Eur J Cell Biol 2012; 91: 496-505 [PMID: 22093287 DOI: 10.1016/j.ejcb.2011.09.008]
26. Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006; 108: 3204-3209 [PMID: 16835372]
27. Verga Falzacappa MV, Vujic Spasic M, Kessler R, Stolte J, Hentze MW, Muckenthaler MU. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood 2007; 109: 353-358 [PMID: 16946298]
28. Pietrangelo A, Dierssen U, Valli L, Garuti C, Rump A, Corradini E, Ernst M, Klein C, Trautwein C. STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterology 2007; 132: 294-300 [PMID: 17241879]
29. Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science 1996; 272: 1336-1339 [PMID: 8650544]
30. Seol W, Chung M, Moore DD. Novel receptor interaction and repression domains in the orphan receptor SHP. Mol Cell Biol 1997; 17: 7126-7131 [PMID: 9372944]
31. Kim YD, Kim YH, Cho YM, Kim DK, Ahn SW, Lee JM, Chanda D, Shong M, Lee CH, Choi HS. Metformin ameliorates IL-6-induced hepatic insulin resistance via induction of orphan nuclear receptor small heterodimer partner (SHP) in mouse models. Diabetologia 2012; 55: 1482-1494 [PMID: 22349108 DOI: 10.1007/s00125-012-2494-4]
32. Yuk JM, Shin DM, Lee HM, Kim JJ, Kim SW, Jin HS, Yang CS, Park KA, Chanda D, Kim DK, Huang SM, Lee SK, Lee CH, Kim JM, Song CH, Lee SY, Hur GM, Moore DD, Choi HS, Jo EK. The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors. Nat Immunol 2011; 12: 742-751 [PMID: 21725320 DOI: 10.1038/ni.2064]
33. Gerjevic LN, Liu N, Lu S, Harrison-Findik DD. Alcohol Activates TGF-Beta but Inhibits BMP Receptor-Mediated Smad Signaling and Smad4 Binding to Hepcidin Promoter in the Liver. Int J Hepatol 2012; 2012: 459278 [PMID: 22121494 DOI: 10.1155/2012/459278]
34. Harrison-Findik DD, Klein E, Evans J, Gollan J. Regulation of liver hepcidin expression by alcohol in vivo does not involve Kupffer cell activation or TNF-alpha signaling. Am J Physiol Gastrointest Liver Physiol 2009; 296: G112-G118 [PMID: 19008338]
35. Gerjevic LN, Lu S, Chaky JP, Harrison-Findik DD. Regulation of heme oxygenase expression by alcohol, hypoxia and oxidative stress. World J Biol Chem 2011; 2: 252-260 [PMID: 22216371 DOI: 10.4331/wjbc.v2.i12.252]
36. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282: 2085-2088 [PMID: 9851930]
37. Reigstad CS, Lundén GO, Felin J, Bäckhed F. Regulation of serum amyloid A3 (SAA3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota. PLoS One 2009; 4: e5842 [PMID: 19513118 DOI: 10.1371/journal.pone.0005842]
38. Tsukamoto H, Takei Y, McClain CJ, Joshi-Barve S, Hill D, Schmidt J, Deaciuc I, Barve S, Colell A, Garcia-Ruiz C, Kaplowitz N, Fernandez-Checa JC, Yokoyama H, Okamura Y, Nakamura Y, Ishii H, Chawla RK, Barve S, Joshi-Barve S, Watson W, Nelson W, Lin M, Ohata M, Motomura K, Enomoto N, Ikejima K, Kitamura T, Oide H, Hirose M, Bradford BU, Rivera CA, Kono H, Peter S, Yamashina S, Konno A, Ishikawa M, Shimizu H, Sato N, Thurman R. How is the liver primed or sensitized for alcoholic liver disease? Alcohol Clin Exp Res 2001; 25: 171S-181S [PMID: 11391068]
39. Kohgo Y, Ohtake T, Ikuta K, Suzuki Y, Hosoki Y, Saito H, Kato J. Iron accumulation in alcoholic liver diseases. Alcohol Clin Exp Res 2005; 29: 189S-193S [PMID: 16344607]
40. Chen J, Kunos G, Gao B. Ethanol rapidly inhibits IL-6-activated STAT3 and C/EBP mRNA expression in freshly isolated rat hepatocytes. FEBS Lett 1999; 457: 162-168 [PMID: 10486586]
41. Greenhill CJ, Rose-John S, Lissilaa R, Ferlin W, Ernst M, Hertzog PJ, Mansell A, Jenkins BJ. IL-6 trans-signaling modulates TLR4-dependent inflammatory responses via STAT3. J Immunol 2011; 186: 1199-1208 [PMID: 21148800 DOI: 10.4049/jimmunol.1002971]
42. Yamawaki Y, Kimura H, Hosoi T, Ozawa K. MyD88 plays a key role in LPS-induced Stat3 activation in the hypothalamus. Am J Physiol Regul Integr Comp Physiol 2010; 298: R403-R410 [PMID: 19955495 DOI: 10.1152/ajpregu.00395.2009]
43. Wang Y, Abarbanell AM, Herrmann JL, Weil BR, Manukyan MC, Poynter JA, Meldrum DR. TLR4 inhibits mesenchymal stem cell (MSC) STAT3 activation and thereby exerts deleterious effects on MSC-mediated cardioprotection. PLoS One 2010; 5: e14206 [PMID: 21151968 DOI: 10.1371/journal.pone.0014206]
44. Darnell JE. STATs and gene regulation. Science 1997; 277: 1630-1635 [PMID: 9287210]
45. Decker T, Kovarik P. Serine phosphorylation of STATs. Oncogene 2000; 19: 2628-2637 [PMID: 10851062 DOI: 10.1038/sj.onc.1203481]
46. Kim YS, Han CY, Kim SW, Kim JH, Lee SK, Jung DJ, Park SY, Kang H, Choi HS, Lee JW, Pak YK. The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-kappa b in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7. J Biol Chem 2001; 276: 33736-33740 [PMID: 11448950 DOI: 10.1074/jbc.M101977200]
47. Gyamfi MA, Wan YJ. Pathogenesis of alcoholic liver disease: the role of nuclear receptors. Exp Biol Med (Maywood) 2010; 235: 547-560 [PMID: 20463294 DOI: 10.1258/ebm.2009.009249]